Polycomb repressive complex 2 regulates normal hematopoietic stem cell function in a developmental-stage-specific manner

Cell Stem Cell. 2014 Jan 2;14(1):68-80. doi: 10.1016/j.stem.2013.10.001. Epub 2013 Nov 14.


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-stage-specific requirements for canonical PRC2 complexes in normal HSC function.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult Stem Cells / cytology
  • Adult Stem Cells / metabolism*
  • Animals
  • Animals, Newborn
  • Biomarkers / metabolism
  • Bone Marrow / metabolism*
  • Cell Differentiation
  • Cell Proliferation
  • Cells, Cultured
  • Chromatin Immunoprecipitation
  • Cyclin-Dependent Kinase Inhibitor p16
  • Flow Cytometry
  • Gene Expression Profiling
  • Gene Expression Regulation, Developmental*
  • Hematopoietic Stem Cells / cytology
  • Hematopoietic Stem Cells / metabolism*
  • Liver / cytology
  • Liver / metabolism*
  • Mice
  • Mice, Knockout
  • Oligonucleotide Array Sequence Analysis
  • Polycomb Repressive Complex 2 / genetics
  • Polycomb Repressive Complex 2 / metabolism*
  • Polycomb Repressive Complex 2 / physiology
  • RNA, Messenger / genetics
  • Real-Time Polymerase Chain Reaction
  • Reverse Transcriptase Polymerase Chain Reaction


  • Biomarkers
  • Cdkn2a protein, mouse
  • Cyclin-Dependent Kinase Inhibitor p16
  • Eed protein, mouse
  • RNA, Messenger
  • Polycomb Repressive Complex 2