The histone demethylase UTX regulates stem cell migration and hematopoiesis.

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.

journal_name

Blood

journal_title

Blood

authors

Thieme S,Gyárfás T,Richter C,Özhan G,Fu J,Alexopoulou D,Muders MH,Michalk I,Jakob C,Dahl A,Klink B,Bandola J,Bachmann M,Schröck E,Buchholz F,Stewart AF,Weidinger G,Anastassiadis K,Brenner S

doi

10.1182/blood-2012-08-452003

subject

Has Abstract

pub_date

2013-03-28 00:00:00

pages

2462-73

issue

13

eissn

0006-4971

issn

1528-0020

pii

blood-2012-08-452003

journal_volume

121

pub_type

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