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The adult human testis transcriptional cell atlas

Guo, Jingtao and Grow, Edward J. and Mlcochova, Hana and Maher, Geoffrey J. and Lindskog, Cecilia and Nie, Xichen and Guo, Yixuan and Takei, Yodai and Yun, Jina and Cai, Long and Kim, Robin and Carrell, Douglas T. and Goriely, Anne and Hotaling, James M. and Cairns, Bradley R. (2018) The adult human testis transcriptional cell atlas. Cell Research, 28 (12). pp. 1141-1157. ISSN 1001-0602. PMCID PMC6274646. https://resolver.caltech.edu/CaltechAUTHORS:20181023-084128561

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Abstract

Human adult spermatogenesis balances spermatogonial stem cell (SSC) self-renewal and differentiation, alongside complex germ cell-niche interactions, to ensure long-term fertility and faithful genome propagation. Here, we performed single-cell RNA sequencing of ~6500 testicular cells from young adults. We found five niche/somatic cell types (Leydig, myoid, Sertoli, endothelial, macrophage), and observed germline-niche interactions and key human-mouse differences. Spermatogenesis, including meiosis, was reconstructed computationally, revealing sequential coding, non-coding, and repeat-element transcriptional signatures. Interestingly, we identified five discrete transcriptional/developmental spermatogonial states, including a novel early SSC state, termed State 0. Epigenetic features and nascent transcription analyses suggested developmental plasticity within spermatogonial States. To understand the origin of State 0, we profiled testicular cells from infants, and identified distinct similarities between adult State 0 and infant SSCs. Overall, our datasets describe key transcriptional and epigenetic signatures of the normal adult human testis, and provide new insights into germ cell developmental transitions and plasticity.


Item Type:Article
Related URLs:
URLURL TypeDescription
https://doi.org/10.1038/s41422-018-0099-2DOIArticle
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6274646PubMed CentralArticle
ORCID:
AuthorORCID
Maher, Geoffrey J.0000-0001-7135-4824
Cai, Long0000-0002-7154-5361
Goriely, Anne0000-0001-9229-7216
Cairns, Bradley R.0000-0002-9864-8811
Additional Information:© 2018 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 30 August 2018; Revised 07 September 2018; Accepted 19 September 2018; Published 12 October 2018. We thank Brian Dalley and Opal Allen for sequencing expertise, Chris Conley and Tim Parnell for bioinformatics assistance, James Marvin for flow cytometry assistance, and Intermountain Donor Service staff for sample handling. Financial support was from Howard Hughes Medical Institute to B.R.C.; P30CA042014 to Huntsman Cancer Institute core facilities from the National Cancer Institute. Flow cytometry core was supported by the National Center for Research Resources of the National Institutes of Health under Award Number 1S10RR026802–01. The Wellcome, UK (Senior Investigator Award 102731 to Prof. Andrew Wilkie) supports A.G., G.J.M., and H.M.; the Wolfson Imaging Center (Oxford) is supported by the WIMM Strategic Alliance (G0902418 and MC_UU_12025). C.L. is supported by the Knut and Alice Wallenberg Foundation. L.C. is supported by NIH U01EB021240. Data and software availability: The accession number for all sequencing data reported in this paper is GEO: GSE120508. Further information and requests for reagents should be directed to and will be fulfilled by the Lead Contact, Bradley R. Cairns (brad.cairns@hci.utah.edu). Author Contributions: B.R.C. and J.G. conceived the project, designed the genomics and analysis experiments, and advised on other sections. J.G. conducted genomics experiments and computational analyses with help from E.J.G. Sample acquisition was led by J.M.H. and R.K. with input from D.T.C., B.R.C., and J.G. Samples were transferred and processed by J.G., Y.G., X.N. and E.J.G. Y.T., J.Y., and L.C. led the design and execution mRNA seqFISH. C.L. provided HPA antibodies. A.G. contributed to project design and led protein validation efforts. H.M. and G.J.M. performed protein immunostaining. J.G., A.G., and B.R.C. wrote the manuscript, with input from all authors. The authors declare no competing interests.
Funders:
Funding AgencyGrant Number
Howard Hughes Medical Institute (HHMI)UNSPECIFIED
NIHP30CA042014
NIH1S10RR026802-01
Wellcome Trust102731
University of OxfordG0902418
University of OxfordMC_UU_12025
Weatherall Institute of Molecular MedicineUNSPECIFIED
Knut and Alice Wallenberg FoundationUNSPECIFIED
NIHU01EB021240
Issue or Number:12
PubMed Central ID:PMC6274646
Record Number:CaltechAUTHORS:20181023-084128561
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20181023-084128561
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:90346
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:23 Oct 2018 21:51
Last Modified:03 Oct 2019 20:24

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