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Publication : Notch Signaling in Nestin-Expressing Cells in the Bone Marrow Maintains Erythropoiesis via Macrophage Integrity.

First Author  Sakamoto T Year  2019
Journal  Stem Cells Volume  37
Issue  7 Pages  924-936
PubMed ID  30932281 Mgi Jnum  J:291354
Mgi Id  MGI:6446654 Doi  10.1002/stem.3011
Citation  Sakamoto T, et al. (2019) Notch Signaling in Nestin-Expressing Cells in the Bone Marrow Maintains Erythropoiesis via Macrophage Integrity. Stem Cells 37(7):924-936
abstractText  Notch signaling plays pivotal roles in both hematopoietic stem/progenitor and their niche cells. Myeloproliferative phenotypes are induced by disruption of Notch signaling in nonhematopoietic bone marrow (BM) cells. Nestin-expressing cells in the BM reportedly represent a component of the hematopoietic stem cell niche. We established mice in which rare Nestin-expressing cells in the BM were marked by green fluorescent protein, and Notch signaling was conditionally disrupted in these cells specifically. We observed impairment of erythropoiesis in the BM accompanying splenomegaly with BM hematopoietic programs in other lineages undisturbed. Transplantation experiments revealed that the microenvironmental rather than the hematopoietic cells were attributable to these phenotypes. We further found that the erythroid-island-forming ability of BM central macrophages was compromised along with the transcriptional upregulation of interleukin-6. Various Inflammatory conditions hamper BM erythropoiesis, which often accompanies extramedullary hematopoiesis. The mouse model demonstrated here may be of relevance to this common pathophysiologic condition. Stem Cells 2019;37:924-936.
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