The transcription factor Tfcp2l1 promotes primordial germ cell-like cell specification of pluripotent stem cells
| Autor: | Yuting Li, Junxiang Ji, Meng Zhang, Qian Ban, Xinbao Zhang, Xiaoxiao Wang, Yan Zhang, Shou-Dong Ye, Xiaofeng Li, Xin Wang |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
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 |
| Zdroj: | The Journal of Biological Chemistry |
| ISSN: | 1083-351X |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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