Transcriptomics

Dataset Information

8

PCGF6, a polycomb group protein, regulates mesodermal lineage differentiation in murine ES cells and functions in iPS reprogramming


ABSTRACT: Polycomb group (PcG) proteins comprise a large group of evolutionary conserved factors with essential roles for embryonic development and adult stem cell function. PcG proteins constitute two main multiprotein polycomb repressive complexes (PRC1 and PRC2) that operate in a hierarchical manner to silence gene expression. Functionally distinct PRC1 complexes are defined by Polycomb group RING finger protein (PCGF) paralogs. So far, six PCGF paralogs (PCGF1-6) have been identified but paralog-specific functions are not well understood. In our studies, we observed that Pcgf6 showed the highest expression level in undifferentiated murine embryonic stem cells (ESCs), blastocysts and testes. When ESCs differentiated, Pcgf6 expression strongly declined. To further investigate Pcgf6 biology, we established dox-inducible shRNA knockdown (KD) ESCs. Following Pcgf6 KD in ESCs the expression of pluripotency genes decreased, while mesodermal- and spermatogenesis-specific genes were de-repressed. Concomitantly with the elevated expression of mesodermal lineage markers, Pcgf6 KD ESCs showed increased hemangioblastic and hematopoietic activities. Finally, PCGF6 replaced SOX2 but not KLF4 or c-MYC in the generation of germline-competent iPS cells. Forced expression of Pcgf6 in OSKM-driven reprogramming increases iPS efficiency while Pcgf6 KD reduces the formation of ESC-like colonies. Together, these analyses show that Pcgf6 is non-redundantly involved in maintaining the pluripotent nature of ESCs and functions in iPS reprogramming. 6 samples were hybridized GeneChip Mouse Gene 1.0 ST Arrays (Affymetrix)

ORGANISM(S): Mus musculus  

SUBMITTER: Albrecht M Müller   Qiong Lin  Daniela Zdzieblo  Matthias Becker  Xiaoli Li  Martin Zenke 

PROVIDER: E-GEOD-56126 | ArrayExpress | 2014-09-26

SECONDARY ACCESSION(S): GSE56126PRJNA242519

REPOSITORIES: GEO, ArrayExpress

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Publications

Pcgf6, a polycomb group protein, regulates mesodermal lineage differentiation in murine ESCs and functions in iPS reprogramming.

Zdzieblo D D   Li X X   Lin Q Q   Zenke M M   Illich D J DJ   Becker M M   Müller A M AM  

Stem cells (Dayton, Ohio) 20141201 12


Polycomb group (PcG) proteins comprise evolutionary conserved factors with essential functions for embryonic development and adult stem cells. PcG proteins constitute two main multiprotein polycomb repressive complexes (PRC1 and PRC2) that operate in a hierarchical manner to silence gene transcription. Functionally distinct PRC1 complexes are defined by Polycomb group RING finger protein (Pcgf) paralogs. So far, six Pcgf paralogs (Pcgf1-6) have been identified as defining components of different  ...[more]

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