RESUMO
The glycoprotein (Gp) IIb/IIIa integrin, also called CD41, is the platelet receptor for fibrinogen and several other extracellular matrix molecules. Recent evidence suggests that its expression is much wider in the hematopoietic system than was previously thought. To investigate the precise expression of the CD41 antigen during megakaryocyte (MK) differentiation, CD34(+) cells from cord blood and mobilized blood cells from adults were grown for 6 days in the presence of stem cell factor and thrombopoietin. Two different pathways of differentiation were observed: one in the adult and one in the neonate cells. In the neonate samples, early MK differentiation proceeded from CD34(+)CD41(-) through a CD34(-)CD41(+)CD42(-) stage of differentiation to more mature cells. In contrast, in the adult samples, CD41 and CD42 were co-expressed on a CD34(+) cell. The rare CD34(+)CD41(+)CD42(-) cell subset in neonates was not committed to MK differentiation but contained cells with all myeloid and lymphoid potentialities along with long-term culture initiating cells (LTC-ICs) and nonobese diabetic/severe combined immune-deficient repopulating cells. In the adult samples, the CD34(+)CD41(+)CD42(-) subset was enriched in MK progenitors, but also contained erythroid progenitors, rare myeloid progenitors, and some LTC-ICs. All together, these results demonstrate that the CD41 antigen is expressed at a low level on primitive hematopoietic cells with a myeloid and lymphoid potential and that its expression is ontogenically regulated, leading to marked differences in the surface antigenic properties of differentiating megakaryocytic cells from neonates and adults. (Blood. 2001;97:2023-2030)
Assuntos
Envelhecimento/genética , Regulação da Expressão Gênica no Desenvolvimento , Células-Tronco Hematopoéticas/metabolismo , Megacariócitos/metabolismo , Complexo Glicoproteico GPIIb-IIIa de Plaquetas/biossíntese , Adulto , Animais , Células Sanguíneas/citologia , Células Sanguíneas/metabolismo , Diferenciação Celular/genética , Linhagem da Célula , Separação Celular , Sangue Fetal/citologia , Transplante de Células-Tronco Hematopoéticas , Células-Tronco Hematopoéticas/citologia , Humanos , Recém-Nascido , Células Matadoras Naturais/citologia , Leucaférese , Subpopulações de Linfócitos/citologia , Megacariócitos/citologia , Camundongos , Camundongos Endogâmicos NOD , Camundongos SCID , Técnicas de Cultura de Órgãos , Complexo Glicoproteico GPIIb-IIIa de Plaquetas/genética , Timo/citologia , Timo/embriologiaRESUMO
To elucidate the role of helix-loop-helix (HLH) Id proteins in hematopoietic differentiation, we used a model of embryonic stem (ES) cell differentiation in vitro which gives access not only to hematopoietic myeloid progenitor cells but also to the more primitive blast colony-forming cell (BL-CFC), the in vitro equivalent of the hemangioblast that gives rise to blast cell colonies in the presence of VEGF. We first demonstrated that ES cell-derived blast cell colonies could be used as a model to study hematopoietic differentiation and maturation. We next established the expression profile of Id genes in this model. Transcripts of the four Id genes were present in ES cells. Id1, Id3 and Id4 gene expression was down-regulated during the development of blast cell colonies while that of Id2 was maintained. Thus, Id1, Id3, and Id4 proteins are candidates for being negative regulators of hematopoiesis in the model of hematopoietic ES cell differentiation in vitro.