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Single-cell transcriptomics identifies CD44 as a marker and regulator of endothelial to haematopoietic transition

Oatley, Morgan and Vargel Bölükbası, Özge and Svensson, Valentine and Shvartsman, Maya and Ganter, Kerstin and Zirngibl, Katharina and Pavlovich, Polina V. and Milchevskaya, Vladislava and Foteva, Vladimira and Natarajan, Kedar N. and Baying, Bianka and Benes, Vladimir and Patil, Kiran R. and Teichmann, Sarah A. and Lancrin, Christophe (2020) Single-cell transcriptomics identifies CD44 as a marker and regulator of endothelial to haematopoietic transition. Nature Communications, 11 . Art. No. 586. ISSN 2041-1723. PMCID PMC6989687. https://resolver.caltech.edu/CaltechAUTHORS:20181030-105949740

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Abstract

The endothelial to haematopoietic transition (EHT) is the process whereby haemogenic endothelium differentiates into haematopoietic stem and progenitor cells (HSPCs). The intermediary steps of this process are unclear, in particular the identity of endothelial cells that give rise to HSPCs is unknown. Using single-cell transcriptome analysis and antibody screening we identified CD44 as a new marker of EHT enabling us to isolate robustly the different stages of EHT in the aorta gonad mesonephros (AGM) region. This allowed us to provide a very detailed phenotypical and transcriptional profile for haemogenic endothelial cells, characterising them with high expression of genes related to Notch signalling, TGFbeta/BMP antagonists (Smad6, Smad7 and Bmper) and a downregulation of genes related to glycolysis and the TCA cycle. Moreover, we demonstrated that by inhibiting the interaction between CD44 and its ligand hyaluronan we could block EHT, identifying a new regulator of HSPC development.


Item Type:Article
Related URLs:
URLURL TypeDescription
https://doi.org/10.1038/s41467-019-14171-5DOIArticle
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6989687/PubMed CentralArticle
https://doi.org/10.1101/338178DOIDiscussion Paper
ORCID:
AuthorORCID
Vargel Bölükbası, Özge0000-0003-4013-6343
Svensson, Valentine0000-0002-9217-2330
Natarajan, Kedar N.0000-0002-9264-1280
Benes, Vladimir0000-0002-0352-2547
Patil, Kiran R.0000-0002-6166-8640
Teichmann, Sarah A.0000-0002-6294-6366
Lancrin, Christophe0000-0003-0028-7374
Alternate Title:Single-cell transcriptomics identifies CD44 as a new marker and regulator of haematopoietic stem cells development
Additional Information:© 2020 The Author(s). This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. Received 27 July 2018; Accepted 18 December 2019; Published 29 January 2020. We thank Kalina Stantcheva and Cora Chadick (EMBL Rome FACS Facility, Italy) for cell sorting; Andreas Buness (EMBL Rome Bioinformatics Services, Italy), Artem Adamov (EMBL, Italy) and Tallulah Andrews (Wellcome Trust Sanger Institute, UK) for help with bioinformatics analysis; Paul Collier (EMBL Genomics Core Facility, Germany) for bulk RNA-seq; Radvilė Prialgauskaitė (EMBL Rome) for help with immunofluorescence analysis; Gisela Luz (Patil Group, EMBL, Germany) for scientific illustration; Inke Näthke (University of Dundee, Scotland), Paul Heppenstall (EMBL, Italy) and Alexander Aulehla (EMBL, Germany) for fruitful scientific discussions. The European Molecular Biology Laboratory and the Wellcome Trust supported this work. Data availability: The source data underlying Figs. 2a, e, 4b, 6c, 8c, f, 9b, c, f and Supplementary Fig. 17 are provided as a Source Data file. All the expression data supporting the results reported in the article can be found in Supplementary Data 1–8. In addition, the sc-RNA-seq raw data are accessible from the ArrayExpress respository (E-MTAB-6987) and the bulk RNA-seq raw data were deposited at the NCBI Gene Expression Omnibus (GSE128971). Author Contributions: M.O.: conceptualization, formal analysis, investigation, and visualization, writing—original draft, writing—review and editing. Ö.V.B.: conceptualization, formal analysis, investigation, visualization, writing—review and editing. V.S.: formal analysis, visualization, writing—review and editing. M.S.: investigation, formal analysis, writing—review and editing. K.G.: investigation, visualization, writing—review and editing. K.Z.: formal analysis, visualization, writing—review and editing. P.V.P.: formal analysis, writing—review and editing. V.M.: formal analysis, writing—review and editing. V.F.: investigation, writing—review and editing. K.N.N.: investigation, writing—review and editing. B.B.: investigation, writing—review and editing. V.B., supervision, writing—review and editing. K.R.P.: supervision, investigation, writing— review and editing. S.A.T.: supervision, investigation, writing—review and editing. C.L.: conceptualization, formal analysis, supervision, investigation, visualization, methodology, writing—original draft, project administration, writing—review and editing. The authors declare no competing interests. Peer review information: Nature Communications thanks the anonymous reviewer(s) for their contribution to the peer review of this work. Peer reviewer reports are available.
Funders:
Funding AgencyGrant Number
European Molecular Biology Laboratory (EMBL)UNSPECIFIED
Wellcome TrustUNSPECIFIED
Subject Keywords:Computational biology and bioinformatics; Haematopoietic stem cells; Transcriptomics
PubMed Central ID:PMC6989687
Record Number:CaltechAUTHORS:20181030-105949740
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20181030-105949740
Official Citation:Oatley, M., Bölükbası, Ö.V., Svensson, V. et al. Single-cell transcriptomics identifies CD44 as a marker and regulator of endothelial to haematopoietic transition. Nat Commun 11, 586 (2020). https://doi.org/10.1038/s41467-019-14171-5
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:90502
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:30 Oct 2018 18:17
Last Modified:02 Apr 2020 17:39

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