TY - JOUR
T1 - The adult human testis transcriptional cell atlas
AU - Guo, Jingtao
AU - Grow, Edward J.
AU - Mlcochova, Hana
AU - Maher, Geoffrey J.
AU - Lindskog, Cecilia
AU - Nie, Xichen
AU - Guo, Yixuan
AU - Takei, Yodai
AU - Yun, Jina
AU - Cai, Long
AU - Kim, Robin
AU - Carrell, Douglas T.
AU - Goriely, Anne
AU - Hotaling, James M.
AU - Cairns, Bradley R.
N1 - Funding Information:
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.
Publisher Copyright:
© 2018, The Author(s).
PY - 2018/12/1
Y1 - 2018/12/1
N2 - 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.
AB - 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.
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U2 - 10.1038/s41422-018-0099-2
DO - 10.1038/s41422-018-0099-2
M3 - Article
C2 - 30315278
AN - SCOPUS:85054924353
VL - 28
SP - 1141
EP - 1157
JO - Cell Research
JF - Cell Research
SN - 1001-0602
IS - 12
ER -