دورية أكاديمية
The opposing roles of the mTOR signaling pathway in different phases of human umbilical cord blood-derived CD34+ cell erythropoiesis
| العنوان: | The opposing roles of the mTOR signaling pathway in different phases of human umbilical cord blood-derived CD34+ cell erythropoiesis |
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| المؤلفون: | Liu, Qian, Luo, Linhong, Ren, Chunhong, Zou, Muping, Yang, Siqin, Cai, Bozhi, Wu, Libiao, Wang, Yunsheng, Fu, Shan, Hua, Xu, Tang, Nianping, Huang, Shiping, Huang, Xianxi, Xin, Wen, Chen, Feiheng, Zhang, Xin |
| المساهمون: | National Nature Science Foundation of China, Special funds for public research and capacity building in Guangdong, 2020 Li Ka Shing Foundation Cross-Disciplinary Research Grant, Grant for Key Disciplinary Project of Clinical Medicine under the Guangdong High-level University Development Program, Trans Dream Fund for Life Science |
| المصدر: | Stem Cells ; volume 38, issue 11, page 1492-1505 ; ISSN 1066-5099 1549-4918 |
| بيانات النشر: | Oxford University Press (OUP) |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | Cell Biology, Developmental Biology, Molecular Medicine |
| الوصف: | As an indispensable, even lifesaving practice, red blood cell (RBC) transfusion is challenging due to several issues, including supply shortage, immune incompatibility, and blood-borne infections since donated blood is the only source of RBCs. Although large-scale in vitro production of functional RBCs from human stem cells is a promising alternative, so far, no such system has been reported to produce clinically transfusable RBCs due to the poor understanding of mechanisms of human erythropoiesis, which is essential for the optimization of in vitro erythrocyte generation system. We previously reported that inhibition of mammalian target of rapamycin (mTOR) signaling significantly decreased the percentage of erythroid progenitor cells in the bone marrow of wild-type mice. In contrast, rapamycin treatment remarkably improved terminal maturation of erythroblasts and anemia in a mouse model of β-thalassemia. In the present study, we investigated the effect of mTOR inhibition with rapamycin from different time points on human umbilical cord blood-derived CD34+ cell erythropoiesis in vitro and the underlying mechanisms. Our data showed that rapamycin treatment significantly suppressed erythroid colony formation in the commitment/proliferation phase of erythropoiesis through inhibition of cell-cycle progression and proliferation. In contrast, during the maturation phase of erythropoiesis, mTOR inhibition dramatically promoted enucleation and mitochondrial clearance by enhancing autophagy. Collectively, our results suggest contrasting roles for mTOR in regulating different phases of human erythropoiesis. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| DOI: | 10.1002/stem.3268 |
| الإتاحة: | https://doi.org/10.1002/stem.3268Test https://academic.oup.com/stmcls/article-pdf/38/11/1492/42611881/stmcls_38_11_1492.pdfTest |
| حقوق: | http://creativecommons.org/licenses/by-nc/4.0Test/ ; http://creativecommons.org/licenses/by-nc/4.0Test/ ; http://doi.wiley.com/10.1002/tdm_license_1.1Test |
| رقم الانضمام: | edsbas.AEC62CBB |
| قاعدة البيانات: | BASE |
| DOI: | 10.1002/stem.3268 |
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