The histone demethylase UTX regulates stem cell migration and hematopoiesis

Sebastian Thieme, Tobias Gyárfás, Cornelia Richter, Günes Özhan, Jun Fu, Dimitra Alexopoulou, Michael H. Muders, Irene Michalk, Christiane Jakob, Andreas Dahl, Barbara Klink, Joanna Bandoła, Michael Bachmann, Evelin Schröck, Frank Buchholz, A. Francis Stewart, Gilbert Weidinger, Konstantinos Anastassiadis, Sebastian Brenner*

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

80 Citations (Scopus)

Abstract

Regulated migration of hematopoietic stem cells is fundamental for hematopoiesis. The molecular mechanisms underlying stem cell trafficking are poorly defined. Based on a short hairpin RNA library and stromal cell-derived factor-1 (SDF-1) migration screening assay, we identified the histone 3 lysine 27 demethylase UTX (Kdm6a) as a novel regulator for hematopoietic cell migration. Using hematopoietic stem and progenitor cells from our conditional UTX knockout (KO) mice, we were able to confirm the regulatory function of UTX on cell migration. Moreover, adult female conditional UTX KO mice displayed myelodysplasia and splenic erythropoiesis, whereas UTX KO males showed no phenotype. During development, all UTX KO female and a portion of UTX KO male embryos developed a cardiac defect, cranioschisis, and died in utero. Therefore, UTY, the male homolog of UTX, can compensate for UTX in adults and partially during development. Additionally, we found that UTX knockdown in zebrafish significantly impairs SDF-1/CXCR4-dependent migration of primordial germ cells. Our data suggest that UTX is a critical regulator for stem cell migration and hematopoiesis.

Original languageEnglish
Pages (from-to)2462-2473
Number of pages12
JournalBlood
Volume121
Issue number13
DOIs
Publication statusPublished - 2013
Externally publishedYes

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