Differentiation of hematopoietic stem cell and myeloid populations by ATP is modulated by cytokines

dc.contributor.authorBarbosa, Christiano Marcello Vaz [UNIFESP]
dc.contributor.authorLeon, Carlos Márcio Moura Ponce de [UNIFESP]
dc.contributor.authorNogueira Filho, Pedro Antonio [UNIFESP]
dc.contributor.authorWasinski, Frederick [UNIFESP]
dc.contributor.authorAraújo, Ronaldo de Carvalho [UNIFESP]
dc.contributor.authorMiranda, Antonio [UNIFESP]
dc.contributor.authorFerreira, Alice Teixeira [UNIFESP]
dc.contributor.authorParedes-Gamero, Edgar Julian [UNIFESP]
dc.contributor.institutionUniversidade Federal de São Paulo (UNIFESP)
dc.date.accessioned2016-01-24T14:16:47Z
dc.date.available2016-01-24T14:16:47Z
dc.date.issued2011-06-01
dc.description.abstractExtracellular nucleotides are emerging as important regulators of inflammation, cell proliferation and differentiation in a variety of tissues, including the hematopoietic system. in this study, the role of ATP was investigated during murine hematopoiesis. ATP was able to reduce the percentage of hematopoietic stem cells (HSCs), common myeloid progenitors and granulocyte-macrophage progenitors (GMPs), whereas differentiation into megakaryocyte-erythroid progenitors was not affected. in addition, in vivo administration of ATP to mice reduced the number of GMPs, but increased the number of Gr-1(+)Mac-1(+) myeloid cells. ATP also induced an increased proliferation rate and reduced Notch expression in HSCs and impaired HSC-mediated bone marrow reconstitution in sublethally irradiated mice. Moreover, the effects elicited by ATP were inhibited by suramin, a P2 receptor antagonist, and BAPTA, an intracellular Ca(2+) chelator. We further investigated whether the presence of cytokines might modulate the observed ATP-induced differentiation. Treatment of cells with cytokines (stem cell factor, interleukin-3 and granulocyte-monocyte colony stimulator factor) before ATP stimulation led to reduced ATP-dependent differentiation in long-term bone marrow cultures, thereby restoring the ability of HSCs to reconstitute hematopoiesis. Thus, our data suggest that ATP induces the differentiation of murine HSCs into the myeloid lineage and that this effect can be modulated by cytokines. Cell Death and Disease (2011) 2, e165; doi:10.1038/cddis.2011.49; published online 2 June 2011en
dc.description.affiliationUniversidade Federal de São Paulo, Dept Biofis, BR-04023062 São Paulo, Brazil
dc.description.affiliationUnifespUniversidade Federal de São Paulo, Dept Biofis, BR-04023062 São Paulo, Brazil
dc.description.affiliationUnifespUniversidade Federal de São Paulo, Dept Bioquim, BR-04044020 São Paulo, Brazil
dc.description.sourceWeb of Science
dc.description.sponsorshipFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)pt
dc.description.sponsorshipIDFAPESP: 2007/58589-9pt
dc.format.extent10
dc.identifierhttps://dx.doi.org/10.1038/cddis.2011.49
dc.identifier.citationCell Death & Disease. London: Nature Publishing Group, v. 2, 10 p., 2011.
dc.identifier.doi10.1038/cddis.2011.49
dc.identifier.issn2041-4889
dc.identifier.urihttps://repositorio.unifesp.br/handle/11600/33721
dc.identifier.wosWOS:000292243000001
dc.language.isoeng
dc.publisherNature Publishing Group
dc.relation.ispartofCell Death & Disease
dc.rightsinfo:eu-repo/semantics/openAccess
dc.subjectATPen
dc.subjectP2 receptorsen
dc.subjectHematopoietic stem cellen
dc.subjectDifferentiationen
dc.subjectMyeloiden
dc.subjectCytokinesen
dc.titleDifferentiation of hematopoietic stem cell and myeloid populations by ATP is modulated by cytokinesen
dc.typeinfo:eu-repo/semantics/article
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