Journal
HUMAN REPRODUCTION UPDATE
Volume 28, Issue 3, Pages 313-345Publisher
OXFORD UNIV PRESS
DOI: 10.1093/humupd/dmac002
Keywords
gametogenesis; transcription factors; infertility; germ cell; germ cell tumors; gene mutations; transcriptional profiling; single-cell RNA-sequencing; pluripotent stem cells; in vitro differentiation
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Funding
- National Institute of Health [1R01HD096026]
- National Natural Science Foundation of China [32070830]
- Fundamental Research Funds from University of Science and Technology of China [WK9110000141, YD9100002007]
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This article discusses the important role of transcription factors in reproductive development, focusing specifically on the transcriptional mechanisms of human reproductive development. By studying the transcriptional network components of human germ cells, deeper insights into human infertility and reproductive disorders can be gained, potentially contributing to the development of novel treatments for infertility.
The pathways of gametogenesis encompass elaborate cellular specialization accompanied by precise partitioning of the genome content in order to produce fully matured spermatozoa and oocytes. Transcription factors are an important class of molecules that function in gametogenesis to regulate intrinsic gene expression programs, play essential roles in specifying (or determining) germ cell fate and assist in guiding full maturation of germ cells and maintenance of their populations. Moreover, in order to reinforce or redirect cell fate in vitro, it is transcription factors that are most frequently induced, over-expressed or activated. Many reviews have focused on the molecular development and genetics of gametogenesis, in vivo and in vitro, in model organisms and in humans, including several recent comprehensive reviews: here, we focus specifically on the role of transcription factors. Recent advances in stem cell biology and multi-omic studies have enabled deeper investigation into the unique transcriptional mechanisms of human reproductive development. Moreover, as methods continually improve, in vitro differentiation of germ cells can provide the platform for robust gain- and loss-of-function genetic analyses. These analyses are delineating unique and shared human germ cell transcriptional network components that, together with somatic lineage specifiers and pluripotency transcription factors, function in transitions from pluripotent stem cells to gametes. This grand theme review offers additional insight into human infertility and reproductive disorders that are linked predominantly to defects in the transcription factor networks and thus may potentially contribute to the development of novel treatments for infertility.
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