Hematopoietic defects in response to reduced Arhgap21

Hematopoietic defects in response to reduced Arhgap21

Author Xavier-Ferrucio, Juliana Google Scholar
Ricon, Lauremilia Google Scholar
Vieira, Karla Google Scholar
Longhini, Ana Leda Google Scholar
Lazarini, Mariana Autor UNIFESP Google Scholar
Bigarella, Carolina Louzao Google Scholar
Franchi, Gilberto, Jr. Google Scholar
Krause, Diane S. Google Scholar
Saad, Sara T. O. Google Scholar
Abstract Arhgap21 is a member of the Rho GTPase activating protein (RhoGAP) family, which function as negative regulators of Rho GTPases. Arhgap21 has been implicated in adhesion and migration of cancer cells. However, the role of Arhgap21 has never been investigated in hematopoietic cells. Herein, we evaluated functional aspects of hematopoietic stem and progenitor cells (HSPC) using a haploinsufficient (Arhgap21(+/-)) mouse. Our results show that Arhgap21(+/-) mice have an increased frequency of phenotypic HSC, impaired ability to form progenitor colonies in vitro and decreased hematopoietic engraftment in vivo, along with a decrease in LSK cell frequency during serial bone marrow transplantation. Arhgap21(+/-) hematopoietic progenitor cells have impaired adhesion and enhanced mobilization of immature LSK and myeloid progenitors. Arhgap21(+/-) mice also exhibit reduced erythroid commitment and differentiation, which was recapitulated in human primary cells, in which knockdown of ARHGAP21 in CMP and MEP resulted in decreased erythroid commitment. Finally, we observed enhanced RhoC activity in the bone marrow cells of Arhgap21(+/-) mice, indicating that Arhgap21 functions in hematopoiesis may be at least partially mediated by RhoC inactivation. (c) 2017 The Authors. Published by Elsevier B.V.
Keywords Arhgap21
Hematopoiesis
Erythroid cells
Hematopoietic stem and progenitor cells
Fate decision
xmlui.dri2xhtml.METS-1.0.item-coverage Amsterdam
Language English
Sponsor FAPESP
CNPq (INCT-Sangue)
National Institutes of Health
Yale Cooperative Center of Excellence in Hematology
Grant number FAPESP: 2009/08908-6
FAPESP: 2010/50682-2
FAPESP: 2011/51959-0
National Institutes of Health: DK086267
National Institutes of Health: DK094934
Yale Cooperative Center of Excellence in Hematology: 1U54DK106857
Date 2018
Published in Stem Cell Research. Amsterdam, v. 26, p. 17-27, 2018.
ISSN 1873-5061 (Sherpa/Romeo, impact factor)
Publisher Elsevier Science Bv
Extent 17-27
Origin http://dx.doi.org/10.1016/j.scr.2017.11.014
Access rights Closed access
Type Article
Web of Science ID WOS:000425879600003
URI https://repositorio.unifesp.br/handle/11600/53854

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