ESPEYB17 7. Puberty Basic Science (8 abstracts)
7.9. The dynamic transcriptional cell atlas of testis development during human puberty
Guo J , Nie X , Giebler M , Mlcochova H , Wang Y , Grow EJ , Donor Connect , Kim R , Tharmalingam M , Matilionyte G , Lindskog C , Carrell DT , Mitchell RT , Goriely A , Hotaling JM & Cairns BR
To read the full abstract: Cell Stem Cell vol. 26,2 (2020): 262–276.e4. doi: https://www.sciencedirect.com/science/article/pii/S1934590919305235?via%3Dihub
This paper describes a transcriptional analysis of human spermatogonial stem cells during puberty and the involvement of testosterone in Sertoli cell maturation.
The testis is one of the few organs that defines most of its cell types, physiology, and function after birth. During puberty, major changes occur, such as proliferation and maturation of niche cells, spermatogonial differentiation, and modulation of hormonal signaling to finally allow spermatogenesis (1). Our understanding of the molecular and genetic mechanisms involved in these dramatic changes are limited to rodent studies, while fundamental differences exist between humans and rodents regarding the onset of spermatogenesis (2).
Here, the authors describe a transcriptional cell atlas of the developing human testis during puberty, generated using Single-cell RNA sequencing. This technique allows the simultaneous examination of thousands of individual cells, representing the entire organ, without the need for prior sorting or enrichment procedures (3). They profiled 10 000 single-cell transcriptomes from whole-testes of four juvenile boys (7, 11, 13, and 14 years old) and compared these data to previously published data in one infant (1 year old) and one adult (25 years old). In addition, in order to explore the role of testosterone in the adult testis, they examined the expression profiles of testes from two adult transfemales who had undergone long-term suppression of testosterone. They determined distinctive phases of germ cell differentiation during puberty and observed that cell maturation could be reversed with testosterone suppression. Importantly, two modes of computational analysis allowed the identification of a common progenitor for Leydig and myoid cells prior to puberty. They also reported major differences between mice and humans regarding the markers for somatic cell development and their timing of appearance.
In summary, this study provides new insights into the development of human spermatogonial stem cells and their niche during puberty. A website has been designed to access the data: https://humantestisatlas.shinyapps.io/humantestisatlas1/.
References:
1. Koskenniemi JJ, Virtanen HE, Toppari J. (2017). Testicular growth and development in puberty. Curr. Opin. Endocrinol. Diabetes Obes. 24, 215–224.
2. Tharmalingam MD, Jorgensen A, Mitchell RT. (2018). Experimental models of testicular development and function using human tissue and cells. Mol. Cell. Endocrinol. 468, 95–110.
3. Birnbaum KD. (2018). Power in Numbers: Single-Cell RNA-Seq Strategies to Dissect Complex Tissues. Annu. Rev. Genet. 52, 203–221.
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ESPE Yearbook of Paediatric Endocrinology
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