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Intestinal stem cell proliferation and tissue homeostasis are monitored by the chromatin remodeling factor Kismet/CHD7

9 May 18

Speaker: Louis Gervais, Ph.D Researcher, Stem Cell and Tissue Homeostasis team in the Department of DevelopmentalBiology and Cancer at the Institut Curie, Paris, France, and member of IRB Barcelona Alumni.



Organizers: IRB Barcelona

Date: Wednesday, May 9, 15:00h

Place: Aula Fèlix Serratosa, Parc Científic de Barcelona

Host: Jordi Casanova, IBMB-CSIC, IRB Barcelona


Chromatin modulation is widely believed to participate to the control of gene expression programs regulating stem cell identity, proliferation and differentiation. Consistent with this notion, distinct chromatin states are established during cell lineage differentiation and act to limit the developmental potential of differentiated cells. In pathological context such as human tumors, genes impacting chromatin structure are frequently mutated. However, the role of epigenetic regulation in adult stem cells and tissue homeostasis remains less-well understood. Using the Drosophila intestine as a model to identify new factors regulating tissue homeostasis and adult stem cell activity, we found that inactivation of the chromatin remodeling factor kismet results in a strong increase in relative number and density of intestinal stem cells (ISC) due to their abnormal proliferation. Kismet is the fly homologue of the mammalian CHD7 a member of the chromodomain-helicase-DNA binding (CHD) subfamily of ATP-dependent chromatin remodeling factors. Mutations in CHD7 are the major cause of CHARGE syndrome, a congenital disease in human. To understand Kismet's role in adult stem cells, we determined which genes are bound by Kismet in the ISC using genome wide mapping of Kismet protein with targeted DamID. Our findings suggest that aberrant activation of EGFR pathway occurs upon kismet inactivation driving stem cell overproliferation. We propose that Kismet establishes a specific gene expression profile essential to limit the effects of mitogenic proliferation signals, and therefore serves as an important regulator of ISC proliferation. Our work highlights the importance of maintaining correct chromatin state in tissue specific stem cells.


Cell and Developmental Biology Programme Seminar