Agenome-wideRNAi screen reveals determinants of human embryonic stem cell identity
简介:The derivation of human ES cells (hESCs) from human blastocysts
represents one of the milestones in stem cell biology1. The full
potential of hESCs in research and clinical applications requires a
detailed understandi简介:The derivation of human ES cells (hESCs) from human blastocysts
represents one of the milestones in stem cell biology1. The full
potential of hESCs in research and clinical applications requires a
detailed understanding of the genetic network that governs the
unique properties of hESCs. Here, we report a genome-wide RNA
interference screen to identify geneswhich regulate self-renewal and
pluripotency properties in hESCs. Interestingly, functionally distinct
complexes involved in transcriptional regulation and chromatin
remodelling are among the factors identified in the screen.
To understand the roles of these potential regulators of hESCs, we
studied transcription factor PRDM14 to gain new insights into its
functional roles in the regulation of pluripotency. We showed that
PRDM14 regulates directly the expression of key pluripotency gene
POU5F1 through its proximal enhancer. Genome-wide location
profiling experiments revealed that PRDM14 colocalized extensively
with other key transcription factors such as OCT4, NANOG
and SOX2, indicating that PRDM14 is integrated into the core
transcriptional regulatory network. More importantly, in a gainof-
function assay, we showed that PRDM14 is able to enhance the
efficiency of reprogramming of human fibroblasts in conjunction
with OCT4, SOX2 and KLF4. Altogether, our study uncovers a
wealth of novel hESC regulators wherein PRDM14 exemplifies a
key transcription factor required for the maintenance of hESC identity
and the reacquisition of pluripotency in human somatic cells.详细>