1. ROBO1 deficiency impairs HSPC homeostasis and erythropoiesis via CDC42 and predicts poor prognosis in MDS.
- Author
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Jia-Cheng Jin, Bing-Yi Chen, Chu-Han Deng, Jia-Nan Chen, Feng Xu, Ying Tao, Cheng-Long Hu, Chun-Hui Xu, Bin-He Chang, Yong Wang, Ming-Yue Fei, Ping Liu, Peng-Cheng Yu, Zi-Juan Li, Xi-Ya Li, Shu-Bei Chen, Yi-Lun Jiang, Xin-Chi Chen, Li-Juan Zong, and Jia-Ying Zhang
- Subjects
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CELL cycle proteins , *ERYTHROPOIESIS , *HEMATOPOIESIS , *HOMEOSTASIS , *HEMATOPOIETIC stem cells , *HEMATOLOGIC malignancies , *MYELODYSPLASTIC syndromes - Abstract
Myelodysplastic syndrome (MDS) is a group of clonal hematopoietic neoplasms originating from hematopoietic stem progenitor cells (HSPCs). We previously identified frequent roundabout guidance receptor 1 (ROBO1) mutations in patients with MDS, while the exact role of ROBO1 in hematopoiesis remains poorly delineated. Here, we report that ROBO1 deficiency confers MDS-like disease with anemia and multilineage dysplasia in mice and predicts poor prognosis in patients with MDS. More specifically, Robo1 deficiency impairs HSPC homeostasis and disrupts HSPC pool, especially the reduction of megakaryocyte erythroid progenitors, which causes a blockage in the early stages of erythropoiesis in mice. Mechanistically, transcriptional profiling indicates that Cdc42, a member of the Rho-guanosine triphosphatase family, acts as a downstream target gene for Robo1 in HSPCs. Overexpression of Cdc42 partially restores the self-renewal and erythropoiesis of HSPCs in Robo1-deficient mice. Collectively, our result implicates the essential role of ROBO1 in maintaining HSPC homeostasis and erythropoiesis via CDC42. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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