Divergent roles for KLF4 and TFCP2L1 in naive ground state pluripotency and human primordial germ cell development

G V Hancock; W Liu; L Peretz; D Chen; J J Gell; A J Collier; J R Zamudio; K Plath; A T Clark

doi:10.1016/j.scr.2021.102493

Divergent roles for KLF4 and TFCP2L1 in naive ground state pluripotency and human primordial germ cell development

Stem Cell Res. 2021 Aug:55:102493. doi: 10.1016/j.scr.2021.102493. Epub 2021 Aug 8.

Authors

G V Hancock¹, W Liu², L Peretz³, D Chen⁴, J J Gell⁵, A J Collier⁶, J R Zamudio³, K Plath⁷, A T Clark⁸

Affiliations

¹ Department of Molecular Cell and Developmental Biology, University of California, Los Angeles, CA, USA; Molecular Biology Institute, University of California, Los Angeles, CA, USA; Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, CA, USA.
² Zhejiang University-University of Edinburgh Institute, Zhejiang University School of Medicine, Hangzhou 310058, PR China.
³ Department of Molecular Cell and Developmental Biology, University of California, Los Angeles, CA, USA.
⁴ Department of Molecular Cell and Developmental Biology, University of California, Los Angeles, CA, USA; Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, CA, USA.
⁵ Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, CA, USA; David Geffen School of Medicine, Department of Pediatrics, Division of Hematology-Oncology, Los Angeles, CA 90095, USA; Jonsson Comprehensive Cancer Center, University of California, Los Angeles, CA, USA.
⁶ Department of Biological Chemistry, David Geffen School of Medicine, Los Angeles, CA, USA.
⁷ Molecular Biology Institute, University of California, Los Angeles, CA, USA; Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, CA, USA; Department of Biological Chemistry, David Geffen School of Medicine, Los Angeles, CA, USA.
⁸ Department of Molecular Cell and Developmental Biology, University of California, Los Angeles, CA, USA; Molecular Biology Institute, University of California, Los Angeles, CA, USA; Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, CA, USA; Jonsson Comprehensive Cancer Center, University of California, Los Angeles, CA, USA. Electronic address: clarka@ucla.edu.

Abstract

During embryo development, human primordial germ cells (hPGCs) express a naive gene expression program with similarities to pre-implantation naive epiblast (EPI) cells and naive human embryonic stem cells (hESCs). Previous studies have shown that TFAP2C is required for establishing naive gene expression in these cell types, however the role of additional naive transcription factors in hPGC biology is not known. Here, we show that unlike TFAP2C, the naive transcription factors KLF4 and TFCP2L1 are not required for induction of hPGC-like cells (hPGCLCs) from hESCs, and they have no role in establishing and maintaining a naive-like gene expression program in hPGCLCs with extended time in culture. Taken together, our results suggest a model whereby the molecular mechanisms that drive naive gene expression in hPGCs/hPGCLCs are distinct from those in the naive EPI/hESCs.

Keywords: KLF4; PGCs; Pluripotency; Primordial Germ Cells; Stem cells; TFCP2L1; hPGCs.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Cell Differentiation
Germ Cells* / metabolism
Human Embryonic Stem Cells* / metabolism
Humans
Kruppel-Like Factor 4
Repressor Proteins / metabolism
Transcription Factors / genetics
Transcriptome

Substances

KLF4 protein, human
Kruppel-Like Factor 4
Repressor Proteins
TFCP2L1 protein, human
Transcription Factors

Abstract

Publication types

MeSH terms

Substances

Grants and funding