TY - JOUR
T1 - Transcriptional metabolic reprogramming implements meiotic fate decision in mouse testicular germ cells
AU - Zhang, Xiaoyu
AU - Liu, Yan
AU - Sosa, Froylan
AU - Gunewardena, Sumedha
AU - Crawford, Peter A.
AU - Zielen, Amanda C.
AU - Orwig, Kyle E.
AU - Wang, Ning
N1 - Publisher Copyright:
© 2023 The Author(s)
PY - 2023/7/25
Y1 - 2023/7/25
N2 - Nutrient starvation drives yeast meiosis, whereas retinoic acid (RA) is required for mammalian meiosis through its germline target Stra8. Here, by using single-cell transcriptomic analysis of wild-type and Stra8-deficient juvenile mouse germ cells, our data show that the expression of nutrient transporter genes, including Slc7a5, Slc38a2, and Slc2a1, is downregulated in germ cells during meiotic initiation, and this process requires Stra8, which binds to these genes and induces their H3K27 deacetylation. Consequently, Stra8-deficient germ cells sustain glutamine and glucose uptake in response to RA and exhibit hyperactive mTORC1/protein kinase A (PKA) activities. Importantly, expression of Slc38a2, a glutamine importer, is negatively correlated with meiotic genes in the GTEx dataset, and Slc38a2 knockdown downregulates mTORC1/PKA activities and induces meiotic gene expression. Thus, our study indicates that RA via Stra8, a chordate morphogen pathway, induces meiosis partially by generating a conserved nutrient restriction signal in mammalian germ cells by downregulating their nutrient transporter expression.
AB - Nutrient starvation drives yeast meiosis, whereas retinoic acid (RA) is required for mammalian meiosis through its germline target Stra8. Here, by using single-cell transcriptomic analysis of wild-type and Stra8-deficient juvenile mouse germ cells, our data show that the expression of nutrient transporter genes, including Slc7a5, Slc38a2, and Slc2a1, is downregulated in germ cells during meiotic initiation, and this process requires Stra8, which binds to these genes and induces their H3K27 deacetylation. Consequently, Stra8-deficient germ cells sustain glutamine and glucose uptake in response to RA and exhibit hyperactive mTORC1/protein kinase A (PKA) activities. Importantly, expression of Slc38a2, a glutamine importer, is negatively correlated with meiotic genes in the GTEx dataset, and Slc38a2 knockdown downregulates mTORC1/PKA activities and induces meiotic gene expression. Thus, our study indicates that RA via Stra8, a chordate morphogen pathway, induces meiosis partially by generating a conserved nutrient restriction signal in mammalian germ cells by downregulating their nutrient transporter expression.
KW - CP: Developmental biology
KW - CP: Molecular biology
KW - germline stem cell, meiosis, meiotic initiation, retinoic acid, Stra8, Slc38a2, spermatogonial stem cell, spermatogenesis, germ cell, nutrient
UR - http://www.scopus.com/inward/record.url?scp=85164315407&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85164315407&partnerID=8YFLogxK
U2 - 10.1016/j.celrep.2023.112749
DO - 10.1016/j.celrep.2023.112749
M3 - Article
C2 - 37405912
AN - SCOPUS:85164315407
SN - 2211-1247
VL - 42
JO - Cell reports
JF - Cell reports
IS - 7
M1 - 112749
ER -