DNA methylation protects hematopoietic stem cell multipotency from myeloerythroid restriction

Research output: Contribution to journalArticle

Abstract

DNA methylation is a dynamic epigenetic mark that undergoes extensive changes during differentiation of self-renewing stem cells. However, whether these changes are the cause or consequence of stem cell fate remains unknown. Here, we show that alternative functional programs of hematopoietic stem cells (HSCs) are governed by gradual differences in methylation levels. Constitutive methylation is essential for HSC self-renewal but dispensable for homing, cell cycle control and suppression of apoptosis. Notably, HSCs from mice with reduced DNA methyltransferase 1 activity cannot suppress key myeloerythroid regulators and thus can differentiate into myeloerythroid, but not lymphoid, progeny. A similar methylation dosage effect controls stem cell function in leukemia. These data identify DNA methylation as an essential epigenetic mechanism to protect stem cells from premature activation of predominant differentiation programs and suggest that methylation dynamics determine stem cell functions in tissue homeostasis and cancer.

Details

Authors
  • Ann-Marie Broeske
  • Lena Vockentanz
  • Shabnam Kharazi
  • Matthew R. Huska
  • Elena Mancini
  • Marina Scheller
  • Christiane Kuhl
  • Andreas Enns
  • Marco Prinz
  • Rudolf Jaenisch
  • Claus Nerlov
  • Achim Leutz
  • Miguel A. Andrade-Navarro
  • Sten Eirik W Jacobsen
  • Frank Rosenbauer
Organisations
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Cell and Molecular Biology
Original languageEnglish
Pages (from-to)1207-U69
JournalNature Genetics
Volume41
Issue number11
Publication statusPublished - 2009
Publication categoryResearch
Peer-reviewedYes

Related research output

Kharazi, S., 2010, Lund Stem Cell Center, Faculty of Medicine, LU. 140 p.

Research output: ThesisDoctoral Thesis (compilation)

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