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

Abhishek Sohni; Kun Tan; Hye Won Song; Dana Burow; Dirk G. de Rooij; Louise Laurent; Tung Chin Hsieh; Raja Rabah; Saher Sue Hammoud; Elena Vicini; Miles F. Wilkinson

doi:10.1016/j.celrep.2019.01.045

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

Abhishek Sohni
, Kun Tan
, Hye Won Song
, Dana Burow
, Dirk G. de Rooij
, Louise Laurent
, Tung Chin Hsieh
, Raja Rabah
, Saher Sue Hammoud
, Elena Vicini
, Miles F. Wilkinson^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

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.

Original language	English
Pages (from-to)	1501-1517.e4
Number of pages	22
Journal	Cell Reports
Volume	26
Issue number	6
DOIs	https://doi.org/10.1016/j.celrep.2019.01.045
Publication status	Published - 5 Feb 2019

Funding

We thank Blue Lake, Song Chen, and Kun Zhang for technical advice for our initial scRNA-seq experiments. We also thank Cuong To and the UCSD Institute for Genomic Medicine for technical support, as well as the San Diego Supercomputer Center for providing data analysis resources. This work was supported by NIH grants R01 GM119128 (M.F.W.) and T32 HD007203 (D.B.), as well as the Lalor Institute (K.T.).

Keywords

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

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10.1016/j.celrep.2019.01.045

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title = "The Neonatal and Adult Human Testis Defined at the Single-Cell Level",

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.",

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doi = "10.1016/j.celrep.2019.01.045",

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AU - Laurent, Louise

AU - Hsieh, Tung Chin

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AU - Hammoud, Saher Sue

AU - Vicini, Elena

AU - Wilkinson, Miles F.

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N2 - 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.

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KW - spermatogonial stem cells

KW - testes

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

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