The Dynamic Transcriptional Cell Atlas of Testis Development during Human Puberty.
Jingtao Guo, Xichen Nie, Maria Giebler, Hana Mlcochova, Yueqi Wang, Edward J Grow, DonorConnect, Robin Kim, Melissa Tharmalingam, Gabriele Matilionyte, Cecilia Lindskog, Douglas T Carrell, Rod T Mitchell, Anne Goriely, James M Hotaling, Bradley R Cairns
Author Information
Jingtao Guo: Howard Hughes Medical Institute, Department of Oncological Sciences and Huntsman Cancer Institute, University of Utah School of Medicine, Salt Lake City, UT 84112, USA; The Andrology Laboratory, Department of Surgery (Andrology/Urology), Center for Reconstructive Urology and Men's Health, University of Utah Health Sciences Center, Salt Lake City, UT 84112, USA.
Xichen Nie: Howard Hughes Medical Institute, Department of Oncological Sciences and Huntsman Cancer Institute, University of Utah School of Medicine, Salt Lake City, UT 84112, USA.
Maria Giebler: Radcliffe Department of Medicine, MRC Weatherall Institute of Molecular Medicine, University of Oxford, Oxford OX39DS, UK.
Hana Mlcochova: Radcliffe Department of Medicine, MRC Weatherall Institute of Molecular Medicine, University of Oxford, Oxford OX39DS, UK.
Yueqi Wang: Department of Computer Science, Columbia University, New York, NY 10027, USA.
Edward J Grow: Howard Hughes Medical Institute, Department of Oncological Sciences and Huntsman Cancer Institute, University of Utah School of Medicine, Salt Lake City, UT 84112, USA.
: DonorConnect, Murray, UT 84107, USA.
Robin Kim: Section of Transplantation, Department of Surgery, University of Utah School of Medicine, Salt Lake City, UT 84132, USA.
Melissa Tharmalingam: MRC Centre for Reproductive Health, The Queen's Medical Research Institute, The University of Edinburgh, Edinburgh EH16 4TJ, UK; Royal Hospital for Children and Young People, Edinburgh EH91LF, UK.
Gabriele Matilionyte: MRC Centre for Reproductive Health, The Queen's Medical Research Institute, The University of Edinburgh, Edinburgh EH16 4TJ, UK; Royal Hospital for Children and Young People, Edinburgh EH91LF, UK.
Cecilia Lindskog: Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, Uppsala 751 85, Sweden.
Douglas T Carrell: The Andrology Laboratory, Department of Surgery (Andrology/Urology), Center for Reconstructive Urology and Men's Health, University of Utah Health Sciences Center, Salt Lake City, UT 84112, USA.
Rod T Mitchell: MRC Centre for Reproductive Health, The Queen's Medical Research Institute, The University of Edinburgh, Edinburgh EH16 4TJ, UK; Royal Hospital for Children and Young People, Edinburgh EH91LF, UK.
Anne Goriely: Radcliffe Department of Medicine, MRC Weatherall Institute of Molecular Medicine, University of Oxford, Oxford OX39DS, UK.
James M Hotaling: The Andrology Laboratory, Department of Surgery (Andrology/Urology), Center for Reconstructive Urology and Men's Health, University of Utah Health Sciences Center, Salt Lake City, UT 84112, USA.
Bradley R Cairns: Howard Hughes Medical Institute, Department of Oncological Sciences and Huntsman Cancer Institute, University of Utah School of Medicine, Salt Lake City, UT 84112, USA. Electronic address: brad.cairns@hci.utah.edu.
The human testis undergoes dramatic developmental and structural changes during puberty, including proliferation and maturation of somatic niche cells, and the onset of spermatogenesis. To characterize this understudied process, we profiled and analyzed single-cell transcriptomes of ∼10,000 testicular cells from four boys spanning puberty and compared them to those of infants and adults. During puberty, undifferentiated spermatogonia sequentially expand and differentiate prior to the initiation of gametogenesis. Notably, we identify a common pre-pubertal progenitor for Leydig and myoid cells and delineate candidate factors controlling pubertal differentiation. Furthermore, pre-pubertal Sertoli cells exhibit two distinct transcriptional states differing in metabolic profiles before converging to an alternative single mature population during puberty. Roles for testosterone in Sertoli cell maturation, antimicrobial peptide secretion, and spermatogonial differentiation are further highlighted through single-cell analysis of testosterone-suppressed transfemale testes. Taken together, our transcriptional atlas of the developing human testis provides multiple insights into developmental changes and key factors accompanying male puberty.
