Notch Signaling in Nestin-Expressing Cells in the Bone Marrow Maintains Erythropoiesis via Macrophage Integrity. (15th April 2019)

• Record Type: Journal Article
• Authors: Sakamoto, Tatsuhiro; Obara, Naoshi; Nishikii, Hidekazu; Kato, Takayasu; Cao-Sy, Luan; Fujimura, Ryosuke; Yagita, Hideo; Sakata-Yanagimoto, Mamiko; Takahashi, Satoru; Chiba, Shigeru
• Is Part Of: Stem cells. Volume 37:Number 7(2019)
• Page Start: 924
• Page End: 936
• Publication Date: 2019-04-15
• Subjects: Bone marrow stromal cells -- Erythropoiesis -- Erythroid differentiation -- Nestin -- Notch; Cloning -- Periodicals; Clone cells -- Periodicals; Stem cells -- Periodicals; Cell Differentiation -- Periodicals; Cell Division -- Periodicals; Clone Cells -- Periodicals; Hematopoietic Stem Cells -- Periodicals; Stem Cells -- Periodicals; 571.84
• DOI: 10.1002/stem.3011
• Languages: English
• ISSNs: 1066-5099

Abstract

Abstract : 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 : Abstract : We showed that Notch signaling in Nestin-expressing MSCs regulates erythroid differentiation in the BM. Disruption of Notch signaling in Nestin-expressing MSCs induced the upregulation of interleukin-6 (IL-6) in central macrophages, and IL-6 can cause the impairment of erythroid-island-forming capacity in central macrophages. The results suggest that the erythropoiesis in the BM is regulated by interaction between the central macrophages and Nestin-expressing MSCs.