Polycomb Cbx family members mediate the balance between haematopoietic stem cell self-renewal and differentiation

Karin Klauke, Visnja Radulovic, Mathilde Broekhuis, Ellen Weersing, Erik Zwart, Sandra Olthof, Martha Ritsema, Sophia Bruggeman, Xudong Wu, Kristian Helin, Leonid Bystrykh, Gerald de Haan*

*Bijbehorende auteur voor dit werk

Onderzoeksoutput: ArticleAcademicpeer review

173 Citaten (Scopus)


The balance between self-renewal and differentiation of adult stem cells is essential for tissue homeostasis. Here we show that in the haematopoietic system this process is governed by polycomb chromobox (Cbx) proteins. Cbx7 is specifically expressed in haematopoietic stem cells (HSCs), and its overexpression enhances self-renewal and induces leukaemia. This effect is dependent on integration into polycomb repressive complex-1 (PRC1) and requires H3K27me3 binding. In contrast, overexpression of Cbx2, Cbx4 or Cbx8 results in differentiation and exhaustion of HSCs. ChIP-sequencing analysis shows that Cbx7 and Cbx8 share most of their targets; we identified approximately 200 differential targets. Whereas genes targeted by Cbx8 are highly expressed in HSCs and become repressed in progenitors, Cbx7 targets show the opposite expression pattern. Thus, Cbx7 preserves HSC self-renewal by repressing progenitor-specific genes. Taken together, the presence of distinct Cbx proteins confers target selectivity to PRC1 and provides a molecular balance between self-renewal and differentiation of HSCs.

Originele taal-2English
Pagina's (van-tot)353-+
Aantal pagina's22
TijdschriftNature Cell Biology
Nummer van het tijdschrift4
StatusPublished - apr.-2013

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