The commitment of the human cell atlas to humanity

Perspective

https://doi.org/10.1038/s41467-024-54306-x

The commitment of the human cell atlas to

humanity

Ido Amit

,KristinArdlie

, Fabiana Arzuaga

, Gordon Awandare

Gary Bader

,AlexanderBernier

, Piero Carninci

7,8

, Stacey Donnelly

Roland Eils

,AlistairR.R.Forrest

, Henry T. Greely

, Roderic Guigo

Nir Hacohen

, Muzlifah Haniffa

, Emily Sarah Kirby

Bartha Maria Knoppers

, Arnold Kriegstein

,EdS.Lein

Sten Linnarsson

,ParthaP.Majumder

18,19

, Miriam Merad

Kerstin Meyer

,MusaM.Mhlanga

, Garry Nolan

NtobekoA.B.Ntusi

,DanaPe

’

, Shyam Prabhakar

Maili Raven-Adams

,AvivRegev

, Orit Rozenblatt-Rosen

,SenjutiSaha

Andrea Saltzman

,AlexK.Shalek

2,29

,JayW.Shin

, Henk Stunnenberg

Sarah A. Teichmann

, Timothy Tickle

, Alexandra-Chloe Villani

Christine Wells

,BarbaraWold

,HuanmingYang

Xiaowei Zhuang

The Human Cell Atlas (HCA) is a global partnership

“

to create comprehensive

reference maps of all human cells

—

the fundamental units of life

–

as a basis for

both understanding human health and d

iagnosing, monitoring, and treating

disease.

”

(

https://www.humancellatlas.org/

) The atlas shall characterize cells

from diverse individuals across the globe to better understand human biology.

HCA proactively considers the priorities of, and bene

fi

ts accrued to, con-

tributing communities. Here, we lay out

principles and act

ion items that have

been adopted to af

fi

rm HCA

’

scommitmenttoequitysothattheatlasisben-

fi

cial to all of humanity.

Humans are made of trillions of cells. Although they all share a basic

physiological architecture, each is unique because of their own in

utero developmental processes, genetic endowment, environmental

exposures and life-experiences. These factors can impact cells and are

important to consider when people get sick. However, it is not always

clear which are the most critical, how they make individuals vulnerable

to speci

fi

c diseases, or how they might be used to select the best

treatment. Further, the full list of factors that can in

fl

uence cells is not

well understood.

The Human Cell Atlas (HCA) is a global partnership of individuals

spanning different backgrounds

—

including biologists, clinicians,

computer scientists, engineers, ethicists, lawyers, educators, science

funders, social workers and others

—

who are actively collaborating to

describe the types and properties of all human cells, using diverse

measurement technologies, especially single-cell and spatial

genomics. HCA

’

s ultimate goal is to create reference maps as a foun-

dation to understand how these cells work individually and together to

form organs and carry out speci

fi

c physiological functions essential to

life, as well as how to use this information to develop improved pre-

ventions, diagnostics and cures for diseases that impact people around

the world. By building a comprehensive encyclopaedia of healthy cells

and their behaviours in individuals, representing various ages, genders

and life-styles, from as many populations and environments as possi-

ble, HCA seeks to better understand human biology, as well as the

contributions of environment and genetics to the ways in which cells

work to keep us well

. However, the task to identify and collect samples

from a diversity of populations is daunting. Currently, geographical

location of residence of participants of a population is the primary

focus, with ongoing efforts to collect from populations with explicitly

diverse ancestries. To systematically address the challenge of de

fi

ning

Received: 26 October 2023

Accepted: 6 November 2024

Check for updates

A full list of af

fi

liations appears at the end of the paper.

e-mail:

ppm@isical.ac.in

Nature Communications

| (2024) 15:10019

1234567890():,;

ancestry, the HCA has set up a Task Force to develop recommenda-

tions for representing diversity in the HCA project, recording diversity-

related metadata and ethically engaging underrepresented popula-

tions; the work of this Task Force is in progress. HCA

’

s Atlas, although

only partially complete, is already beginning to provide understanding

of health and diagnosis, monitoring, and treatment of disease. For

example, in ulcerative colitis, single-cell atlas data enabled the identi-

fi

cation of a rare cell type

–

epithelial M-like cells

–

which are

exceedingly rare in the healthy colon, but expanded signi

fi

cantly in

the in

fl

amed, diseased colon

; further examples can be found in

Rood et al

Until recently, because of technical limitations, it had not been

possible to assess comprehensively the fundamental building blocks

of the human body

–

individual cells

–

in health and disease. With the

technologies that were available previously, comprehensive informa-

tion could only be obtained on the properties of large groups of cells.

Recent scienti

fi

c and technological advances are enabling scientists to

obtain information on single cells, and leading to the construction of

the atlas. However, at present, there is no adequate understanding of

the cell types that make up the different tissues of the human body and

how their relative abundance or other properties vary among a diverse

set of individuals. It is hoped that the single-cell information that HCA

is generating will continue to yield conclusions that provide better

management of health to enhance quality of life by pinpointing pre-

cisely where things go wrong in disease and how to control them.

In considering how this information may impact individuals

around the globe, it is clear that much of the healthcare research

performed to date has been limited in its ability to consider the full

impacts of variations in age, sex, genetic make-up, environmental

exposures or life-experiences

, and that medical breakthroughs have

often not been equally bene

fi

cial to all

. Unfortunately, some previous

scienti

fi

c studies have even been extractive and exploitative, failing to

suf

fi

ciently consider the priorities of, or bene

fi

ts to, contributing

communities. Building on knowledge gained from past international

research consortia and leveraging the momentum of technological

advances in single-cell and spatial genomics, the HCA strives to

advance social and scienti

fi

cbene

fi

t by open participation. Further-

more, it is committed to enhancing global engagement by both (i)

creating an active outreach and education programme to build local

capacity to undertake research projects, and (ii) forging and fostering

local collaborative partnerships so that it can bene

fi

t from diverse

community perspectives and shared approaches to facing complex

challenges in human biology. In collaboration with visual and digital

artists, inventors, designers, local communities and schoolchildren,

the HCA has created an art and science exhibition

–

One Cell at a

Time

–

for the general public to explore the biological and cellular

make-up of the human body

. The HCA considers outreach and edu-

cation as mission critical

–

the help of the global research community is

needed to get it right.

Thepathtoequitableresearch

International health research consortia, unfortunately, often build on

past history of research practices and in doing so may fail to ade-

quately address questions of equity and diversity, including limited

involvement of communities around the world in research design and

implementation. These practices have led to scienti

fi

c bias, as well as

inequities and injustices both in capacity-building and bene

fi

t-sharing

of resources and

fi

ndings

. Furthermore, inadequate involvement of

local communities can lead to underrepresentation of certain

populations

which can, in turn, lead to scienti

fi

c biases in

fi

ndings

stigmatization of groups, and, in extreme cases, systemic racism and

discrimination

In the wake of these realizations, several key players of the

research ecosystem, including scientists, funders, publishers and

institutions, have called for a reform in the way research is done

–

ensure relevant stakeholders are involved throughout the research

lifecycle

. Trust needs to be built with all involved in research, and

local scientists

–

working in institutions in the regions where a project

is being conducted

–

can act as liaisons to do so by ensuring that

science is also relevant to local speci

fi

cities and needs.

Large international consortia and projects involving collection of

large and diverse datasets, such as the HCA, require particular atten-

tion. Indeed, equitable research calls for engagement efforts at various

levels, including with communities, through the entire period of

research; including design, planning, governance and execution

.It

also requires support and enabling of local scientists

–

i.e., researchers

in a de

fi

ned geographical region, including resource-poor regions

–

undertake their own research projects

, which, in turn, contributes

to the collection of diverse datasets representative of global popula-

tions, and dissemination of discoveries and

fi

ndings to local popula-

tions. Such enabling can also help create jobs and opportunities in

science locally, and bring cutting edge approaches to a broader swatch

of research than that of the originating consortium

per se. We hope

that the global information being generated by the HCA will enable a

better understanding of the circumstances that are unique to a com-

munity, or commonly seen around the world. Information generated

from local projects driven by local priorities and conducted by local

scientists (i.e., scientists working in institutions in the region where the

project is being conducted), and assisted by the information provided

by the global collective, will generate conclusions bene

fi

cial to local

communities.

Setting up the human cell atlas and underlying principles

Objectives of the Atlas:

The HCA primarily focuses on cellular variation

in healthy tissues as a reference to understand both health and disease.

There are many different cell types in the human body. Scientists do

not know all of the cell types that compose each organ and their

relative proportions. And, even in the same organ, the proportions of

cell types can vary between, for example, males and females, children

and adults, non-smokers and smokers, Bantu speakers of Africa and

Austro-Asiatic speakers of India and southeast Asia, etc. An under-

standing needs to be developed as to the breadth of cell types, com-

position and states present when genetic, environmental, and

experiential factors vary. This requires collecting cells from various

organs from diverse cohorts of people. By explicitly measuring diver-

sity and variation within

‘

healthy

’

tissues, HCA aims to better under-

stand the range of cells across humans

The HCA has started to collect cells and study the biological

characteristics of each collected cell

–

for example, which genes are

expressed and at what level. This information is enabling scientists to

identify the types of cells and their proportions in various organs of the

human body, and, to estimate the extent of variation that exists across

individuals at a very high resolution

–

at the level of single cells. Having

reference maps with suf

fi

cient variation is a

fi

rst step towards inferring

the possible causes of variation across ancestry, demographic vari-

ables and environmental exposures, understanding biological

mechanisms, and developing disease models and treatments that are

more generalizable to the human population as a whole.

Local involvement and recruitment:

HCA investigators are reach-

ing out globally to various communities to undertake projects driven

by local scientists. HCA membership is globally open to anyone above

16 years of age who agrees to abide by the ethical standards and

principles of the HCA as enshrined in the HCA White Paper (

https://

arxiv.org/abs/1810.05192

) and updates noti

fi

ed on HCA

’

swebsite

(

https://www.humancellatlas.org/

). HCA is reaching out far and wide

to scientists and other interested persons across commu-

nities, ethnicities or ancestries

–

a group of people who share a com-

mon cultural, historical and/or biological background

–

to become

active, contributing members. Currently, there are 3153 members of

the HCA from 97 countries located in nearly all regions of the world

Perspective

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| (2024) 15:10019

(Fig.

; for regularly updated details see

https://www.humancellatlas.

org/learn-more/hca-metrics/

). HCA leadership is committed to

empowering, supporting, and working with, local scientists to help

facilitate this work; for example, helping to provide adequate infor-

mation about HCA to the general members of the community to gain

their con

fi

dence, to train local scientists in methods of single-cell

analyses so they can lead research in this area, to engage with local and

global funders to help increase the amount of

fi

nancial resources

available for HCA research, to foster research collaborations and to

obtain approvals from the local research ethics committees to

undertake HCA studies to foster dedicated and vibrant regional net-

works, including for each of Asia, Latin America, Africa, and the Middle

East, and to ensure that local scientists from around the world are

foremost members and leaders in HCA

’

s top governance bodies and

key working groups. To facilitate engagement of local communities,

the HCA encourages local scientists and other interested persons to

become members of the HCA and actively participate in HCA.

HCA considers the involvement of local partners as crucial for

obtaining tissue samples ethically and studying cells from donors

across the world. HCA further considers that building and maintaining

trust with communities is critical for recruiting research participants

and for the success of HCA. To be clear, the HCA believes that research

should be led by local scientists or individuals who wish to be part of

the HCA and should include members of the speci

fi

c communities on

whom studies are undertaken. The HCA is committed to the success of

these individuals through active partnerships. The HCA is actively

engaged in advocacy for international funding in the lesser-endowed

global regions so that local scientists can participate in HCA research.

Indeed, lack of adequate funding to researchers in many regions of the

world is the most serious impediment to their participation in the HCA;

this impediment needs to be overcome to enhance inclusivity and

diversity. The nature of biological material to be collected should be

determined by the local scienti

fi

c partners and in consultation with the

community. The nature of the information to be generated, stored,

analyzed, and shared with the community and the modalities of con-

duct of these activities are also determined in consultation with local

scientists, members of the community, ethics committees, and other

similar groups of the community. Aside from funding, there are many

additional challenges in expanding HCA activities to many global

regions. These include restrictio

ns on the import of equipment and

reagents, inadequate time and facilities for collection of deep meta-

data, lack of adequately trained personnel to carry out experimental

and computational work for single-cell and spatial genomics, and lack

of specialized equipment and appropriate infrastructure. To overcome

some of these challenges, HCA has organized several dedicated

training workshops and discussion sessions. These include an in-

person Computational and Experimental Design Workshop in Bangkok

in 2024 attended by researchers from 13 countries of the Asia Paci

fi

region, a hybrid HCA symposium for Latin America with centres in

three nodal countries, a Latin America in-person Computational and

Experimental Design Workshop in Chile in 2023, a Computational and

Experimental Design Workshop in Ghana in 2023; Introduction to

Single Cell RNA-Seq Analysis (virtual workshop) in October and

November 2022 in Africa; Single Cell Transcriptomics (virtual work-

shop) in January 2022 in India; and, Single Cell RNA-seq Data Analysis

(virtual workshop) in 2021 in Latin America. Overall, since 2019, 13 such

events have been organized mostly in LMICs, attended by a total of

over 2000 researchers (Table

). HCA continues to partner with its

regional networks on such training efforts.

The leadership of the HCA that initially included a few visionary

scientists has been expanded to include prominent scientists from

nearly every region of the world. Currently, about a quarter of the HCA

leadership (the Organizing Committee) are from Asia, Australia, Latin

America and the Middle East. In addition, the Equity Working Group

–

one of the earliest Working Groups established by the HCA

–

was also

sequentially expanded with members from disparate global regions;

currently 11 of the 15 members are from outside of North America or

Europe.

Fig. 1 | Geographical distribution of locations of members of the Human

Cell Atlas.

Geographical distribution of locations of members of the Human Cell

Atlas, most of whom are scientists engaged in HCA activities or have expressed an

interest to participate in the HCA. (see

https://www.humancellatlas.org/learn-

more/hca-metrics/

for details).

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The HCA has developed a number of regional networks, including

HCA Asia, HCA Latin America and HCA Africa, and research networks

—

such as, the Genetic Diversity Biological Network

—

to ensure that the

effort remains connected

—

and relevant

—

to communities, inter-

nationally. These networks ef

fi

ciently promote engagement of local

communities, co-ordination and dissemination.

Consent and sample collection:

The process of sharing infor-

mation about HCA, especially its goals and expected outcomes, to

ethically enroll informed study participants involves group discus-

sions with local communities in their own languages. Of course,

written informed consent is taken from each volunteer willing to

participate in HCA after the volunteer has understood the risks and

bene

fi

ts of participation, prior to collecting samples with adequate

safeguards in place, making sure to minimize risks and pain asso-

ciated with sample collection. The information provided to each

individual mainly comprises the intent of the project, the bene

fi

tto

be accrued in the long run even if not immediately, how the col-

lected biospecimen and the generated data will be used, stored and

shared, risks of participation and modalities of later withdrawal

from the project. Each collected sample is stored in a vial labelled

with a code. The coding process ensures that

“

direct identi

fi

ers

”

such as name and address are removed, helping to maintain sample

donor anonymity.

The nature of samples collected in a HCA project depends on the

speci

fi

c objectives of the project. Indeed, to create a map of the human

body, different tissue sampling scenarios must be envisaged depend-

ing on the source of the tissue examined and how the sample can be

obtained (e.g., post-mortem sampling, use of leftover clinical/surgical

tissue, adult participants, pediatric participants, etc.). For example,

HCA investigators who are studying the process of infection by SARS-

CoV-2 coronavirus have collected nasal and throat swabs from living

donors as well as post-mortem lung tissue from deceased individuals

who succumbed to COVID-19; those studying the cellular processes

associated with childbirth are collecting cord blood and placenta;

those studying immune-system development are collecting blood;

those studying skin disease are collecting skin tissues, and those

creating cell atlases of internal organs such as the lung are collecting

tissues using bronchoscopy or organ donations which were ultimately

considered inadequate for transplant.

Sample analysis:

The collected samples are processed so that

information can be collected from single cells and nuclei (for single cell

genomics) or tissue sections (for spatial genomics). This process is

performed under the strict supervision of well-trained scientists and

with great care to minimize wastage of collected samples. At this time,

all directly identifying information is removed prior to DNA/RNA

analysis of each cell. HCA recommends that, to the extent possible,

sample analysis be done in a laboratory close to the community col-

lection site by local scientists. The HCA helps facilitate training to

support this. Between 2019 and 2024, the Equity Working Group

(EqWG), created to promote equity in the HCA, has conducted road-

shows, meetings and training programs in Thailand, Brazil, Ethiopia,

India, Ghana, Chile, and two global online training programs on

introduction of single-cell RNA sequence analysis. HCA believes that

efforts should be made to enable the sample-processing laboratories

to be open to visits by study participants and community members.

Scientists should provide explanations to such visitors of the various

stages of sample analysis.

Data collection:

HCA projects are led by scientists who are

designated as principal investigators. Data collected from study

participants and generated from the experiments on samples col-

lected from them are stored in databases controlled by principal

investigators of the study and in publicly-accessible global data-

bases for advancement of science, following strict legal and ethical

standards. Only codes

–

but not

“

direct identi

fi

ers

”

such as name,

address, etc.

–

are used to mark individual participants in these

databases. The data comprise those that are collected from each

participant, such as age at the time of collection, gender, informa-

tion on how the cells were collected, and the primary data gener-

ated in the laboratory, such as levels of expression of genes in single

cells. Depending on the study, some general information about the

study participant

’

s health (e.g., whether the participant has high

blood pressure or has ever been infected with malaria) and envir-

onment (e.g., whether the participant lives in a city or near a humid,

forested area, or whether the participant typically cooks with gas,

Table 1 | Meetings, roadshows and workshops organized by the Human Cell Atlas for researchers in various global regions

Year Nature of Training

Countries from which Scientists

Participated

Theme

No. of Participants

2019 In-person Roadshow

Brazil

Human Cell Atlas: Scienti

fi

c foci and equity

2019 In-person Meeting (held in Addis

Ababa, Ethiopia)

15 countries from various global

regions

Human Cell Atlas: Scienti

fi

c foci, participation and equity 58

2020 On-line Meeting

21 countries of Latin America

Human Cell Atlas: Initiation of activities in Latin America

425

2021 On-line Workshop

24 countries of Latin America

Single-cell RNA_sequencing analysis

410

2022 On-line Workshop

India and Pakistan

Introduction to single-cell transcriptomics methodology

220

2022 On-line Workshop

Various countries of Africa

Introduction to the Human Cell Atlas

136

2022 On-line Symposium

22 countries of Latin America

Introduction to Human Cell Atlas and single-cell tran-

scriptomics methodology

170

2022 On-line Workshop

12 countries of Africa

Introduction to single-cell RNA-sequencing analysis

2022 On-line Workshop

18 countries of Africa

Repeat of the previous workshop on Introduction to single-

cell RNA-sequencing analysis

2023 In-person Workshop

12 countries of Africa

Single-cell RNA_sequencing: Computational and experi-

mental designs

2023 In-person Workshop

7 countries of South America

Human Cell Atlas Latin America: Computational and

Experimental Design Workshop

2023 Online Seminar Series

Sri Lanka

Single-Cell Genomics

163

2024 In-person Workshop (held in

Bangkok, Thailand)

13 countries of the Asia Paci

fi

c region Single-Cell Omics: Computational and Experimental

Design Workshop

2024 Hybrid mode Symposium

3 nodal countries of Latin America

(Chile, Brazil, Mexico)

Human Cell Atlas Latin America Symposium

> 100

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| (2024) 15:10019

charcoal, wood, or another fuel source) might also be recorded.

Altogether, such ancillary information helps scientists understand

the different factors that might in

fl

uence the behavior of genes in

human cells.

The Human Cell Atlas has created a cloud-based Data Portal that

stores data contributed by HCA collaborators. A Data Explorer inter-

face has been created to help researchers

fi

nd and explore HCA

datasets;

https://data.humancellatlas.org

. As determined by the ethics

approval associated with the study, some portions of the data (e.g. the

raw sequencing data) may only be accessible by researchers with

permission of HCA

’

s Data Access Committee through HCA

’

s controlled

access repository.

Data dissemination, access and use:

HCA data are analysed using

statistical, computational and bioinformatic methods. HCA

encourages and supports training and engagement of local HCA

investigators or other persons from the community to participate

equitably in data analysis. HCA researchers have been developing

experimental and computational methods that can be effectively

deployed in different settings and sharing these by organizing local

workshops and scienti

fi

c consultations. After appropriate analyses of

data are completed and conclusions drawn, those general conclu-

sions are conveyed to study participants if they wish to know, or

shared with the community in a summary form through local scien-

tists. The HCA strongly advocates that community meetings be

organized by local scientists and summary results be explained to the

participating communities.

Subsequently, the data

–

stripped of all direct identi

fi

ers but

coded to mark individual participants

–

are placed on a globally-

accessible, public-domain database for the advancement of science

by not only HCA investigators, but by anyone who may be interested

to do so by analyzing the data. Data dissemination in HCA is in

accordance with the Fort Lauderdale principles (

https://www.

genome.gov/Pages/Research/WellcomeReport0303.pdf

); details of

HCA data release policy are provided on the HCA web site (

https://

www.humancellatlas.org/wp-content/uploads/2019/07/2019-Jul-09-

HCA-Data-Release-Policy-v1.0.pdf

). It follows in the footsteps and

ethos of other large-scale resources that were built to share and

disseminate biomedical datasets (particularly

“

omics

”

data) Exam-

ples of these databases include the Human Genome Project

, the

International HapMap Project

, the 1000 Genomes Project

, the

Human Pangenome Project

, the International Cancer Genome

Consortium

, as well as local or regional initiatives such as the UK

Biobank

, AllofUs

, H3Africa

, to name a few.

In some instances, access controls are used to further heighten

the privacy and security guarantees made to research participants. If a

researcher contributes unpublished data, on the request of the

researcher the data can be

“

embargoed

”

until published. Data sharing

practices in health sciences generally propose a spectrum ranging

from controlled (or managed) access data to open data, where data-

sets are made publicly available without restrictions. Under a con-

trolled (or managed) access mechanism, datasets are only accessible

to researchers having met a certain number of prerequisite conditions

(e.g. proposed research is in line with the allowed use of data, research

team has the necessary expertise to handle data, ethics approvals are

in place, etc.) and in many cases, access requests are governed by a

Data Access Committee and subject to a data transfer/sharing agree-

ment. Since its inception, the HCA has favoured an open access data

model, whereby datasets with appropriate permissions (e.g. partici-

pant consent, institutional approvals, etc.) are released in a public,

open access, database. Indeed, this ethos was adopted to enable

equitable, rapid, free and unencumbered access to its resources, which

are developed collaboratively by researchers around the world

However, the HCA also recognises that while ultimately, the objective

of open access is to reduce the barriers to using and sharing data, it can

also unintentionally hinder participation of certain groups, especially

where there are concerns of potential stigmatization

. Therefore, in

an effort to include a wide range of contributions, alongside open

access, HCA has also implemented a

‘

managed access

’

tier whereby

datasets that are more sensitive can be deposited, managed and access

granted to researchers following approval by a centralized HCA Data

Access Committee and signature of a data access agreement between

the approved researcher

’

s institution and the HCA. Since genetic

information collected in the RNA and DNA sequences can sometimes

be used to predict family relationships between donors, HCA

encourages investigators to adopt the best privacy and security

practices prevailing (e.g., GA4GH

“

Data Privacy and Security Policy

”

)

to maintain the databases and promote responsible use of the

HCA data.

Discrimination:

Some biological characteristics are observed to

be similar within family groups, and among communities with similar

ancestries. Regrettably, these similarities and differences have

sometimes been used for racial pro

fi

ling, discrimination and

exploitation. Notable historical examples of misuse of research data

include, for instance, the Tuskegee Syphilis studies

, the Havasupai

Indian Tribe case

, or, more recently, genetic research done without

appropriate consent on DNA samples from Xinjiang (Uyghur

individuals)

and Tibet

. There are many more examples of data/

sample misuse or misinterpretation, often discriminatory in nature,

including attempts and approvals to commercialize drugs based on

“

race

”

Race is a social construct, not a biological one. HCA strongly

opposes the use of biological differences for social discrimination,

which is a violation of fundamental human rights and freedoms.

Instead, all efforts should be made to explain the scienti

fi

cmeaningof

the data and to answer questions from individuals and communities on

how information related to biological differences, including genetic,

types and numbers of cells, among others, might be used with time to

improve the health and well-being of the community. The HCA is aware

that misinterpretation of observed biological patterns could lead to

genetic discrimination

–

a source of exclusion and stigmatization. It

considers racial pro

fi

ling or any form of discrimination to be against

the spirit of the consortium, the purpose of the data collection, and the

ethical conduct that is expected to be followed by the consortium

members. Through its governance, HCA places strong emphasis on

accountability in the ethical conduct of its scienti

fi

cresearch

embodying high levels of quality, equity and integrity.

Conclusion: Implications for Future Biomedical Research

The HCA has embedded its commitment to humanity through various

means, notably by engaging local scientists and other local persons. It

has developed a number of regional networks that facilitate the

organization of local meetings and dissemination events.

The Equity Working Group (EqWG) was created by the HCA in

order to promote and support progress towards equity in the HCA.

The EqWG seeks to engage the global community spanning diverse

geographic and ethnic groups to drive inclusive representation and

participation, and promote equal bene

fi

tfromtheHCA.Sinceits

inception, the EqWG has adopted an

‘

equity in action

’

approach

–

with

its activities centred around empowerment to participate in the HCA

through outreach, education, and training

The Ethics Working Group of the HCA has also supported efforts

in implementing the HCA worldwide,

through the creation of an ethics

toolkit (available online at:

https://www.humancellatlas.org/ethics/

)

This toolkit aims to provide researchers from around the world with

templates (e.g., consent form models, information pamphlets) and

governance documents (e.g., HCA FAQ, data sharing/material transfer

agreements, etc.) in order to implement HCA research in their own

communities and institutions. These were developed to be

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| (2024) 15:10019

‘

internationally interoperable

’

given that legal and ethics standards can

vary in different jurisdictions

It is hoped that the reference maps created by the HCA will help

researchers understand whether every person af

fl

icted with a

disease

–

for example, liver cancer

–

has common biological or cellular

changes in the affected organ. Knowledge gained from this work will

result in a better understanding

of both health and management and

care of individual patients. To achieve this ultimate goal, it is important

that the reference maps re

fl

ect biological and cellular variation present

in various organs among healthy individuals from diverse back-

grounds, including variable genetic ancestries, sex, age, geography,

environment, and lifestyle. Unless there is an understanding of the

extent of variation among healthy persons, it will not be possible to

detect changes that may lead to the disease being studied. For exam-

ple, blood and urine tests could be misleading if they are not calibrated

to the natural range of variation observed in a relevant group of indi-

viduals. The encyclopaedia of cells that is being created by the HCA will

be an important step towards accomplishing the ultimate goal of

providing better care to individual patients, immensely bene

fi

cial to all

of humanity.

The HCA

’

s action-oriented approach to fostering global part-

nerships by highlighting the fundamental goal of bene

fi

tting

humanity (though applying principles of equity, diversity and inclu-

sion) can also serve as a model for other biomedical consortia.

Indeed, both its overall philosophy, as well as tools for implementing

–

for instance, through working groups, online toolkits (e.g., ethics

documentation) and roadshows and training workshops can foster

adoption of common strategies and interoperability between similar

initiatives.

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Acknowledgements

An earlier version of this manuscript was archived on

Open Science

Forum

; DOI 10.17605/OSF.IO/EZVC5;

https://osf.io/sk697/

.Thereis

considerable overlap in the narratives of this manuscript with the

archived version. We have not placed the overlapping text within quotes

and have not referenced the archived

version in this manuscript. We are

grateful to Tracey Andrew, John Randell, Kristine Schwenck, Ellen

Todres and Samantha Wynne, for help, suggestions and support.

Figure

is licensed under Creative Commons CC BY-ND 4.0. This

publication is part of the Human Cell Atlas:

www.humancellatlas.org/

publications/

Author contributions

P.M., A.K. Shalek, and M.M. conceived of the idea of writing this com-

mentary. The

fi

rst draft was prepared by them and supplemented by E.K.

and B.M.K. All authors contributed to the development and writing of

this manuscript.

Competing interests

A.R. is an employee of Genentech, a member of the Roche group, and

has equity in Roche. A.R. was a co-founder and equity holder of Celsius

Therapeutics, is an equity holder in Immunitas, and until July 31, 2020

Perspective

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Nature Communications

| (2024) 15:10019

was an S.A.B. member of Thermo Fisher Scienti

fi

c, Syros Pharmaceu-

ticals, Neogene Therapeutics and Asi

mov. A.R. is an inventor on multiple

patents related to single cell and spatial genomics. All other authors

declare no competing interests.

Additional information

Correspondence

and requests for materials should be addressed to

Partha P. Majumder.

Peer review information

Nature Communications

thanks the anon-

ymous reviewer(s) for their contribution to the peer review of this work.

Reprints and permissions information

is available at

http://www.nature.com/reprints

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’

s note

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isdictional claims in published maps and institutional af

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Weizmann Institute of Science, Rehovot, Israel.

Broad Institute, Cambridge, USA.

Ministry of Science, Technology and Productive Innovation, Buenos

Aires, Argentina.

West African Center for Cell Biology of Infectious Pathogens, University of Ghana, Legon, Ghana.

University of Toronto, Toronto, Canada.

Centre for Genomics and Policy, McGill University, Montreal, Canada.

RIKEN Center for Integrative Medical Sciences, Hokkaido, Japan.

Human Technopole,

Milan, Italy.

BIH@Charité - Center for Digital Health, Berlin, Ethiopia.

Harry Perkins Institute of Medical Research, Perth, Australia.

Stanford Law School,

Stanford University, California, USA.

Center for Genomic Regulation, Universitat Pompeu Fabra, Barcelona, Spain.

Center for Cancer Immunotherapy, Mass

General Hospital, Charlestown, USA.

Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge CB10 1SA, UK.

University of California,

San Fransisco, USA.

University of Washington, Seattle, USA.

Karolinska Institute, Solna, Sweden.

John C. Martin Centre for Liver Research & Innovation,

Kolkata, India.

Indian Statistical Institute, Kolkata, India.

Mount Sinai School of Medicine, New York, USA.

RIMLS-Science, Nijmegen, The Netherlands.

Stanford University School of Medicine, California, USA.

University of Cape Town, South Africa, and SAMRC Extramural Unit on Intersection of Non-

communicable Diseases and Infectious Diseases, Cape Town, South Africa.

Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New

York, USA.

Genome Institute of Singapore, Agency for Science, Technology and Research (A*STAR), Singapore, Singapore.

Global Alliance for Genomics

and Health, Wellcome Sanger Institute, Hinxton, UK.

Human Cell Atlas, South San Francisco, USA.

Child Health Research Foundation, Dhaka, Bangladesh.

Massachusetts Institute of Technology, Boston, USA.

Radboud Institute for Molecular Life Sciences, Nijmegen, The Netherlands.

Massachusetts General

Hospital, Boston, USA.

University of Melbourne, Melbourne, Australia.

California Institute of Technology, California, USA.

BGI-Shenzhen,

Shenzhen, China.

Harvard University, Cambridge, USA.

e-mail:

ppm@isical.ac.in

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| (2024) 15:10019