Poised Lineage Specification in Multipotential Hematopoietic Stem and Progenitor Cells by the Polycomb Protein Bmi1

Hideyuki Oguro, Jin Yuan, Hitoshi Ichikawa, Tomokatsu Ikawa, Satoshi Yamazaki, Hiroshi Kawamoto, Hiromitsu Nakauchi, Atsushi Iwama

研究成果: Article査読

149 被引用数 (Scopus)

抄録

Polycomb group (PcG) proteins are essential regulators of stem cells. PcG and trithorax group proteins mark developmental regulator gene promoters with bivalent domains consisting of overlapping repressive and activating histone modifications to keep them poised for activation in embryonic stem cells. Bmi1, a component of PcG complexes, maintains the self-renewal capacity of adult stem cells, but its role in multipotency remains obscure. Here we show that Bmi1 is critical for multipotency of hematopoietic stem cells (HSCs) and multipotent progenitors (MPPs). B cell lineage developmental regulator genes, Ebf1 and Pax5, appeared to be transcriptionally repressed by bivalent domains before lineage commitment. Loss of Bmi1 resulted in a resolution of bivalent domains at the Ebf1 and Pax5 loci, leading to their premature expression in HSC/MPPs accompanied by accelerated lymphoid specification and a marked reduction in HSC/MPPs. Thus, Bmi1 is required to reinforce bivalent domains at key developmental regulator gene loci to maintain lineage specification poised for activation in adult stem cells.

本文言語English
ページ(範囲)279-286
ページ数8
ジャーナルCell Stem Cell
6
3
DOI
出版ステータスPublished - 05-03-2010
外部発表はい

All Science Journal Classification (ASJC) codes

  • 分子医療
  • 遺伝学
  • 細胞生物学

フィンガープリント

「Poised Lineage Specification in Multipotential Hematopoietic Stem and Progenitor Cells by the Polycomb Protein Bmi1」の研究トピックを掘り下げます。これらがまとまってユニークなフィンガープリントを構成します。

引用スタイル