TY - JOUR
T1 - The histone demethylase UTX regulates stem cell migration and hematopoiesis
AU - Thieme, Sebastian
AU - Gyárfás, Tobias
AU - Richter, Cornelia
AU - Özhan, Günes
AU - Fu, Jun
AU - Alexopoulou, Dimitra
AU - Muders, Michael H.
AU - Michalk, Irene
AU - Jakob, Christiane
AU - Dahl, Andreas
AU - Klink, Barbara
AU - Bandoła, Joanna
AU - Bachmann, Michael
AU - Schröck, Evelin
AU - Buchholz, Frank
AU - Francis Stewart, A.
AU - Weidinger, Gilbert
AU - Anastassiadis, Konstantinos
AU - Brenner, Sebastian
N1 - Publisher Copyright:
© 2013 by The American Society of Hematology.
PY - 2013
Y1 - 2013
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84876470605&partnerID=8YFLogxK
U2 - 10.1182/blood-2012-08-452003
DO - 10.1182/blood-2012-08-452003
M3 - Article
C2 - 23365460
AN - SCOPUS:84876470605
SN - 0006-4971
VL - 121
SP - 2462
EP - 2473
JO - Blood
JF - Blood
IS - 13
ER -