The Dynamic Transcriptional Cell Atlas of Testis Development during Human Puberty

Summary 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.
Graphical Abstract
Highlights • A transcriptional single-cell atlas of the developing testes during human puberty • Distinctive phases of germ cell differentiation occur during puberty • Identification of a common progenitor for Leydig and myoid cells prior to puberty • Partial reversal of Sertoli and germ cell maturation upon testosterone suppression
Guo et al. provide a transcriptional cell atlas of the developing human testis during puberty, revealing dramatic developmental changes in both germ and somatic niche cell lineages. Furthermore, germ cells and Sertoli cells from testosterone-suppressed transfemale testes display partial developmental reversal, revealing critical roles for testosterone in maintaining testis maturation.