1. The transcription factor Tfcp2l1 promotes primordial germ cell-like cell specification of pluripotent stem cells
- Author
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Yuting Li, Junxiang Ji, Meng Zhang, Qian Ban, Xinbao Zhang, Xiaoxiao Wang, Yan Zhang, Shou-Dong Ye, Xiaofeng Li, and Xin Wang
- Subjects
iMeLCs, incipient mesoderm-like cells ,Stem cell factor ,Biochemistry ,Mice ,FACS, fluorescence-activated cell sorting ,Tfcp2l1, transcription factor CP2-like 1 ,Oct4, octamer-binding transcription factor 4 ,Induced pluripotent stem cell ,Prdm14, PR domain zinc finger protein 14 ,Zinc finger ,primordial germ cell–like cells ,LIF, leukemia inhibitory factor ,Wnt signaling pathway ,iPSCs, induced pluripotent stem cells ,qRT-PCR, quantitative real-time PCR ,embryonic stem cells ,KSR, KnockOut Serum Replacement ,Cell biology ,ChIP, chromatin immunoprecipitation ,medicine.anatomical_structure ,EpiSCs, epiblast stem cells ,Germ cell ,Research Article ,Pluripotent Stem Cells ,Transcription Factor AP-2-Gamma ,DOX, doxycycline ,Prdm14 ,Biology ,Cell Line ,Protein Domains ,i-Tfcp2l1, inducible Tfcp2l1 ,PGCs, primordial germ cells ,medicine ,Animals ,Humans ,Molecular Biology ,Transcription factor ,PB, PiggyBac ,EGF, epidermal growth factor ,SCF, stem cell factor ,TFCP2l1 ,BMP, bone morphogenetic protein ,Cell Biology ,ESCs, embryonic stem cells ,Embryonic stem cell ,Repressor Proteins ,Germ Cells ,Blimp1, B lymphocyte–induced maturation protein-1 ,ROCK, Rho-associated protein kinase ,Tfap2c, transcription factor AP-2 gamma ,Wnt, wingless/integrated ,PGCLCs, PGC-like cells ,EpiLCs, epiblast-like cells ,Transcription Factors - Abstract
Primordial germ cells (PGCs) are common ancestors of all germline cells. However, mechanistic understanding of how PGC specification occurs is limited. Here, we identified transcription factor CP2-like 1 (Tfcp2l1), an important pluripotency factor, as a pivotal factor for PGC-like cell (PGCLC) specification. High-throughput sequencing and quantitative real-time PCR analysis showed that Tfcp2l1 expression is gradually increased during mouse and human epiblast differentiation into PGCLCs in vivo and in vitro. Consequently, overexpression of Tfcp2l1 can enhance the specification efficiency even without inductive cytokines in mouse epiblast-like cells derived from embryonic stem cells, while knockdown of Tfcp2l1 significantly inhibits PGCLC generation. Mechanistic studies revealed that Tfcp2l1 exerts its function partially through the direct induction of PR domain zinc finger protein 14, a key PGC marker, as downregulation of the PR domain zinc finger protein 14 transcript can impair the ability of Tfcp2l1 to direct PGCLC commitment. Importantly, we finally demonstrated that the crucial role of the human homolog Tfcp2l1 in promoting PGCLC specification is conserved in human pluripotent stem cells. Together, our data uncover a novel function of Tfcp2l1 in PGCLC fate determination and facilitate a better understanding of germ cell development.
- Published
- 2021