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Cell Rep. 2019 Feb 5;26(6):1501-1517.e4. doi: 10.1016/j.celrep.2019.01.045.

The Neonatal and Adult Human Testis Defined at the Single-Cell Level.

Author information

1
Department of Obstetrics, Gynecology, and Reproductive Sciences, University of California, San Diego, La Jolla, CA 92093, USA.
2
Reproductive Biology Group, Division of Developmental Biology, Department of Biology, Faculty of Science, Utrecht University, 3584 CH Utrecht, the Netherlands.
3
Department of Urology, University of California, San Diego, La Jolla, CA 92103, USA.
4
Pediatric and Perinatal Pathology, Michigan Medicine, CS Mott and VonVoigtlander Women's Hospitals, Ann Arbor, MI 48109-4272, USA.
5
Department of Human Genetics, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
6
Department of Anatomy, Histology, Forensic Medicine and Orthopedic, Section of Histology Sapienza University of Rome, 00161 Rome, Italy.
7
Department of Obstetrics, Gynecology, and Reproductive Sciences, University of California, San Diego, La Jolla, CA 92093, USA; Institute of Genomic Medicine, University of California, San Diego, La Jolla, CA 92093, USA. Electronic address: mfwilkinson@ucsd.edu.

Abstract

Spermatogenesis has been intensely studied in rodents but remains poorly understood in humans. Here, we used single-cell RNA sequencing to analyze human testes. Clustering analysis of neonatal testes reveals several cell subsets, including cell populations with characteristics of primordial germ cells (PGCs) and spermatogonial stem cells (SSCs). In adult testes, we identify four undifferentiated spermatogonia (SPG) clusters, each of which expresses specific marker genes. We identify protein markers for the most primitive SPG state, allowing us to purify this likely SSC-enriched cell subset. We map the timeline of male germ cell development from PGCs through fetal germ cells to differentiating adult SPG stages. We also define somatic cell subsets in both neonatal and adult testes and trace their developmental trajectories. Our data provide a blueprint of the developing human male germline and supporting somatic cells. The PGC-like and SSC markers are candidates to be used for SSC therapy to treat infertility.

KEYWORDS:

Leydig cells; Sertoli cells; germ cells; peritubular myoid cells; primordial germ cells; single-cell RNA sequencing; spermatogenesis; spermatogonia; spermatogonial stem cells; testes

PMID:
30726734
DOI:
10.1016/j.celrep.2019.01.045
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