Hematopoietic defects in response to reduced Arhgap21

Página do item simplificado
dc.citation.volume26
dc.contributor.authorXavier-Ferrucio, Juliana
dc.contributor.authorRicon, Lauremilia
dc.contributor.authorVieira, Karla
dc.contributor.authorLonghini, Ana Leda
dc.contributor.authorLazarini, Mariana [UNIFESP]
dc.contributor.authorBigarella, Carolina Louzao
dc.contributor.authorFranchi, Gilberto, Jr.
dc.contributor.authorKrause, Diane S.
dc.contributor.authorSaad, Sara T. O.
dc.coverageAmsterdam
dc.date.accessioned2020-07-02T18:52:03Z
dc.date.available2020-07-02T18:52:03Z
dc.date.issued2018
dc.description.abstractArhgap21 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.en
dc.description.affiliationUniv Campinas UNICAMP, Inst Nacl Ciencia & Tecnol Sangue, Hematol & Blood Transfus Ctr, Hemoctr, Campinas, SP, Brazil
dc.description.affiliationUniv Fed Sao Paulo, Dept Biol Sci, Diadema, Brazil
dc.description.affiliationUniv Campinas UNICAMP, Fac Med Sci, CIPOI, Oncohematol Child Res Ctr, Campinas, SP, Brazil
dc.description.affiliationYale Sch Med, Dept Lab Med, New Haven, CT USA
dc.description.affiliationXavier-Ferrucio, Juliana
dc.description.affiliationYale Sch Med, Yale Stem Cell Ctr, New Haven, CT USA
dc.description.affiliationUnifespUniv Fed Sao Paulo, Dept Biol Sci, Diadema, Brazil
dc.description.sourceWeb of Science
dc.description.sponsorshipFAPESP
dc.description.sponsorshipCNPq (INCT-Sangue)
dc.description.sponsorshipNational Institutes of Health
dc.description.sponsorshipYale Cooperative Center of Excellence in Hematology
dc.description.sponsorshipIDFAPESP: 2009/08908-6
dc.description.sponsorshipIDFAPESP: 2010/50682-2
dc.description.sponsorshipIDFAPESP: 2011/51959-0
dc.description.sponsorshipIDNational Institutes of Health: DK086267
dc.description.sponsorshipIDNational Institutes of Health: DK094934
dc.description.sponsorshipIDYale Cooperative Center of Excellence in Hematology: 1U54DK106857
dc.format.extent17-27
dc.identifierhttp://dx.doi.org/10.1016/j.scr.2017.11.014
dc.identifier.citationStem Cell Research. Amsterdam, v. 26, p. 17-27, 2018.
dc.identifier.doi10.1016/j.scr.2017.11.014
dc.identifier.fileWOS000425879600003.pdf
dc.identifier.issn1873-5061
dc.identifier.urihttps://repositorio.unifesp.br/handle/11600/53854
dc.identifier.wosWOS:000425879600003
dc.language.isoeng
dc.publisherElsevier Science Bv
dc.relation.ispartofStem Cell Research
dc.rightsinfo:eu-repo/semantics/restrictedAccess
dc.subjectArhgap21en
dc.subjectHematopoiesisen
dc.subjectErythroid cellsen
dc.subjectHematopoietic stem and progenitor cellsen
dc.subjectFate decisionen
dc.titleHematopoietic defects in response to reduced Arhgap21en
dc.typeinfo:eu-repo/semantics/article
Arquivos
Coleções
ICAQF - Artigos