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The transcription factor Tfcp2l1 promotes primordial germ cell-like cell specification of pluripotent stem cells
The transcription factor Tfcp2l1 promotes primordial germ cell-like cell specification of pluripotent stem cells
- Source :
- The Journal of Biological Chemistry
- Publication Year :
- 2021
-
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.
- 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
Subjects
Details
- ISSN :
- 1083351X
- Volume :
- 297
- Issue :
- 4
- Database :
- OpenAIRE
- Journal :
- The Journal of biological chemistry
- Accession number :
- edsair.doi.dedup.....44acb44a05e35b6e07993ad30720ada1