The Dynamic Transcriptional Cell Atlas of Testis Development During Human Puberty

The human testis undergoes dramatic developmental and structural changes during puberty, including proliferation and maturation of niche/somatic cells, and the onset of spermatogenesis. Here, we profiled and analyzed single-cell transcriptomes of ~10,000 testicular cells from four boys spanning puberty, and compared to infants and adults. During puberty, undifferentiated spermatogonia first expand and then differentiate, prior to gametogenesis. Notably, we identify a common pre-pubertal progenitor for Leydig and myoid cells, and reveal candidate factors/pathways for pubertal differentiation. Furthermore, pre-pubertal Sertoli cells form two states that differ in mitochondrial/metabolic transcription, which converge to a single mature population during puberty. Roles for testosterone in Sertoli cell maturation, antimicrobial peptide secretion and spermatogonial differentiation are revealed through analyses of testosterone-suppressed transgender female testis and via in vitro seminiferous tubule culturing. Overall, our transcriptional atlas of the developing human testis provides major insights into developmental changes and key factors/pathways that accompany male puberty. Overall design: Single-cell RNA-seq of testicular cells from different ages of boys in puberty. Testosterone-suppressed transgender female testis samples are included.