The histone demethylase UTX regulates stem cell migration and hematopoiesis
- Authors
- Thieme, S., Gyárfás, T., Richter, C., Özhan, G., Fu, J., Alexopulou, D., Muders, M.H., Michalk, I., Jakob, C., Dahl, A., Klink, B., Bandola, J., Bachmann, M., Schröck, E., Buchholz, F., Stewart, A.F., Weidinger, G., Anastassiadis, K., and Brenner, S.
- ID
- ZDB-PUB-130211-18
- Date
- 2013
- Source
- Blood 121(13): 2462-2473 (Journal)
- Registered Authors
- Özhan, Günes, Weidinger, Gilbert
- Keywords
- none
- MeSH Terms
-
- Female
- Humans
- Gene Expression Regulation, Developmental/physiology
- Cells, Cultured
- Hematopoietic Stem Cells/metabolism
- Hematopoietic Stem Cells/physiology*
- Histone Demethylases/genetics
- Histone Demethylases/metabolism
- Histone Demethylases/physiology*
- Mice, Knockout
- Hematopoiesis/genetics*
- Animals
- Zebrafish/embryology
- Zebrafish/genetics
- Mice, Inbred C57BL
- Embryo, Nonmammalian
- Mice
- Male
- HEK293 Cells
- Cell Movement/genetics*
- Gene Expression Regulation, Enzymologic/physiology
- PubMed
- 23365460 Full text @ Blood
Regulated migration of hematopoietic stem cells is fundamental for hematopoiesis. The molecular mechanisms underlying stem cell trafficking are poorly defined. Based on an shRNA library and SDF-1 migration screening assay, we have 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 homologue of UTX, can partially compensate for UTX in adults as well as 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.