Back to Search
Start Over
Nutrient restriction synergizes with retinoic acid to induce mammalian meiotic initiation in vitro.
- Source :
-
Nature communications [Nat Commun] 2021 Mar 19; Vol. 12 (1), pp. 1758. Date of Electronic Publication: 2021 Mar 19. - Publication Year :
- 2021
-
Abstract
- The molecular machinery and chromosome structures carrying out meiosis are frequently conserved from yeast to mammals. However, signals initiating meiosis appear divergent: while nutrient restriction induces meiosis in the yeast system, retinoic acid (RA) and its target Stra8 have been shown to be necessary but not sufficient to induce meiotic initiation in mammalian germ cells. Here, we use primary culture of mouse undifferentiated spermatogonia without the support of gonadal somatic cells to show that nutrient restriction in combination with RA is sufficient to induce Stra8- and Spo11-dependent meiotic gene and chromosome programs that recapitulate the transcriptomic and cytologic features of in vivo meiosis. We demonstrate that neither nutrient restriction nor RA alone exerts these effects. Moreover, we identify a distinctive network of 11 nutrient restriction-upregulated transcription factor genes, which are associated with early meiosis in vivo and whose expression does not require RA. Our study proposes a conserved model, in which nutrient restriction induces meiotic initiation by upregulating key transcription factor genes for the meiotic gene program and provides an in vitro platform for meiotic induction that could facilitate research and haploid gamete production.
- Subjects :
- Adaptor Proteins, Signal Transducing genetics
Animals
Cells, Cultured
Endodeoxyribonucleases genetics
Gene Expression drug effects
Male
Mammals genetics
Mammals metabolism
Meiosis genetics
Mice, Inbred C57BL
Mice, Inbred DBA
Mice, Knockout
Sequence Analysis, RNA methods
Single-Cell Analysis methods
Spermatogonia cytology
Spermatogonia metabolism
Mice
Adaptor Proteins, Signal Transducing metabolism
Endodeoxyribonucleases metabolism
Meiosis drug effects
Nutrients metabolism
Spermatogonia drug effects
Tretinoin pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 2041-1723
- Volume :
- 12
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Nature communications
- Publication Type :
- Academic Journal
- Accession number :
- 33741948
- Full Text :
- https://doi.org/10.1038/s41467-021-22021-6