Reprogramming of fibroblasts into induced pluripotent stem cells with orphan nuclear receptor Esrrb
简介:The dominant effect of transcription factors in imparting
expanded potency is best exemplified by the reprogramming
of fibroblasts to pluripotent cells using retrovirus-mediated
transduction of defined transcription f简介:The dominant effect of transcription factors in imparting
expanded potency is best exemplified by the reprogramming
of fibroblasts to pluripotent cells using retrovirus-mediated
transduction of defined transcription factors. In the murine
system, Oct4, Sox2, c‑Myc and Klf4 are sufficient to convert
fibroblasts to induced pluripotent stem (iPS) cells that have many
characteristics of embryonic stem (ES) cells. Here we show that
the orphan nuclear receptor Esrrb functions in conjunction with
Oct4 and Sox2 to mediate reprogramming of mouse embryonic
fibroblasts (MEFs) to iPS cells. Esrrb-reprogrammed cells share
similar expression and epigenetic signatures as ES cells. These
cells are also pluripotent and can differentiate in vitro and in vivo
into the three major embryonic cell lineages. Furthermore,
these cells contribute to mouse chimaeras and are germline
transmissible. In ES cells, Esrrb targets many genes involved
in self-renewal and pluripotency. This suggests that Esrrb may
mediate reprogramming through the upregulation of ES-cellspecific
genes. Our findings also indicate that it is possible to
reprogram MEFs without exogenous Klf transcription factors and
link a nuclear receptor to somatic cell reprogramming.详细>