TY - JOUR
T1 - Poised Lineage Specification in Multipotential Hematopoietic Stem and Progenitor Cells by the Polycomb Protein Bmi1
AU - Oguro, Hideyuki
AU - Yuan, Jin
AU - Ichikawa, Hitoshi
AU - Ikawa, Tomokatsu
AU - Yamazaki, Satoshi
AU - Kawamoto, Hiroshi
AU - Nakauchi, Hiromitsu
AU - Iwama, Atsushi
N1 - Funding Information:
We thank Maarten van Lohuizen and Ronald A. DePinho for providing Bmi1 +/− mice and Ink4a +/− mice, respectively, Naohito Nozaki for the Bmi1 antibody, and Yuji Yamazaki for flow cytometric sorting. H.O. is supported by a postdoctoral fellowship from the Japanese Society for the Promotion of Science . This work was supported in part by Grants-in-Aid for Scientific Research (# 20052009 ) and for the Global COE Program (Global Center for Education and Research in Immune System Regulation and Treatment), MEXT, Japan , a Grant-in-Aid for the Core Research for Evolutional Science and Technology (CREST) from the Japan Science and Technology Corporation (JST) , and a grant from the Takeda Science Foundation .
PY - 2010/3/5
Y1 - 2010/3/5
N2 - 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.
AB - 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.
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U2 - 10.1016/j.stem.2010.01.005
DO - 10.1016/j.stem.2010.01.005
M3 - Article
C2 - 20207230
AN - SCOPUS:77449159608
SN - 1934-5909
VL - 6
SP - 279
EP - 286
JO - Cell Stem Cell
JF - Cell Stem Cell
IS - 3
ER -