期刊
CELL STEM CELL
卷 14, 期 1, 页码 68-80出版社
CELL PRESS
DOI: 10.1016/j.stem.2013.10.001
关键词
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资金
- National Institutes of Health [CA105423]
- Harvard Stem Cell Institute Blood Program
- National Institute of Diabetes and Digestive and Kidney Diseases Career Development Award [K01DK093543]
Recent studies point to a pivotal role of Polycomb repressive complex 2 (PRC2) in stem cell function and cancer. Loss-of-function approaches targeting individual PRC2 subunits have, however, generated findings that are difficult to reconcile. Here, we prevent assembly of both Ezh1- and Ezh2-containing PRC2 complexes by conditional deletion of Eed, a core subunit, and assess hematopoiesis. We find that deletion of Eed exhausts adult bone marrow hematopoietic stem cells (HSCs), although fetal liver HSCs are produced in normal numbers. Eed-null neonatal HSCs express HSC signature genes but are defective in maintenance and differentiation. Comparative gene expression profiling revealed that neonatal and adult HSCs lacking Eed upregulated gene sets of conflicting pathways. Deletion of Cdkn2a, a PRC2 target gene, in Eed-null mice enhances hematopoietic stem/progenitor cell (HSPC) survival but fails to restore HSC functions. Taken together, our findings define developmental-stagespecific requirements for canonical PRC2 complexes in normal HSC function.
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