Endothelial Cell-Selective Adhesion Molecule Expression in Hematopoietic Stem-Progenitor Cells Is Essential for Erythropoiesis Recovery after Bone Marrow InjuryReportar como inadecuado




Endothelial Cell-Selective Adhesion Molecule Expression in Hematopoietic Stem-Progenitor Cells Is Essential for Erythropoiesis Recovery after Bone Marrow Injury - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

Numerous red blood cells are generated every second from proliferative progenitor cells under a homeostatic state. Increased erythropoietic activity is required after myelo-suppression as a result of chemo-radio therapies. Our previous study revealed that the endothelial cell-selective adhesion molecule ESAM, an authentic hematopoietic stem cell marker, plays essential roles in stress-induced hematopoiesis. To determine the physiological importance of ESAM in erythroid recovery, ESAM-knockout KO mice were treated with the anti-cancer drug, 5-fluorouracil 5-FU. ESAM-KO mice experienced severe and prolonged anemia after 5-FU treatment compared to wild-type WT mice. Eight days after the 5-FU injection, compared to WT mice, ESAM-KO mice showed reduced numbers of erythroid progenitors in bone marrow BM and spleen, and reticulocytes in peripheral blood. Megakaryocyte-erythrocyte progenitors MEPs from the BM of 5-FU-treated ESAM-KO mice showed reduced burst forming unit-erythrocyte BFU-E capacities than those from WT mice. BM transplantation revealed that hematopoietic stem-progenitor cells from ESAM-KO donors were more sensitive to 5-FU treatment than that from WT donors in the WT host mice. However, hematopoietic cells from WT donors transplanted into ESAM-KO host mice could normally reconstitute the erythroid lineage after a BM injury. These results suggested that ESAM expression in hematopoietic cells, but not environmental cells, is critical for hematopoietic recovery. We also found that 5-FU treatment induces the up-regulation of ESAM in primitive erythroid progenitors and macrophages that do not express ESAM under homeostatic conditions. The phenotypic change seen in macrophages might be functionally involved in the interaction between erythroid progenitors and their niche components during stress-induced acute erythropoiesis. Microarray analyses of primitive erythroid progenitors from 5-FU-treated WT and ESAM-KO mice revealed that various signaling pathways, including the GATA1 system, were impaired in ESAM-KO mice. Thus, our data demonstrate that ESAM expression in hematopoietic progenitors is essential for erythroid recovery after a BM injury.



Autor: Takao Sudo, Takafumi Yokota , Daisuke Okuzaki, Tomoaki Ueda, Michiko Ichii, Tomohiko Ishibashi, Tomomi Isono, Yoko Habuchi, Kenji

Fuente: http://plos.srce.hr/



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