Identification of MS4A3 as a reliable marker for early myeloid differentiation in human hematopoiesis |
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Authors: | Tomohiko Ishibashi Takafumi Yokota Yusuke Satoh Michiko Ichii Takao Sudo Yukiko Doi Tomoaki Ueda Yasuhiro Nagate Yuri Hamanaka Akira Tanimura Sachiko Ezoe Hirohiko Shibayama Kenji Oritani Yuzuru Kanakura |
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Affiliation: | 1. Department of Hematology and Oncology, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan;2. Department of Vascular Physiology, National Cerebral and Cardiovascular Center Research Institute, Suita, Osaka 565-8565, Japan;3. Department of Lifestyle Studies, Kobe Shoin Women''s University, Kobe 657-0015, Japan;4. Department of Immunology and Cell Biology, Graduate School of Medicine and Frontier Biosciences, Osaka University, Suita, Osaka 565-0871, Japan |
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Abstract: | Information of myeloid lineage-related antigen on hematopoietic stem/progenitor cells (HSPCs) is important to clarify the mechanisms regulating hematopoiesis, as well as for the diagnosis and treatment of myeloid malignancies. We previously reported that special AT-rich sequence binding protein 1 (SATB1), a global chromatin organizer, promotes lymphoid differentiation from HSPCs. To search a novel cell surface molecule discriminating early myeloid and lymphoid differentiation, we performed microarray analyses comparing SATB1-overexpressed HSPCs with mock-transduced HSPCs. The results drew our attention to membrane-spanning 4-domains, subfamily A, member 3 (Ms4a3) as the most downregulated molecule in HSPCs with forced overexpression of SATB1. Ms4a3 expression was undetectable in hematopoietic stem cells, but showed a concomitant increase with progressive myeloid differentiation, whereas not only lymphoid but also megakaryocytic-erythrocytic progenitors were entirely devoid of Ms4a3 expression. Further analysis revealed that a subset of CD34+CD38+CD33+ progenitor population in human adult bone marrow expressed MS4A3, and those MS4A3+ progenitors only produced granulocyte/macrophage colonies, losing erythroid colony- and mixed colony-forming capacity. These results suggest that cell surface expression of MS4A3 is useful to distinguish granulocyte/macrophage lineage-committed progenitors from other lineage-related ones in early human hematopoiesis. In conclusion, MS4A3 is useful to monitor early stage of myeloid differentiation in human hematopoiesis. |
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Keywords: | Membrane-spanning 4-domains, subfamily A, member 3 Human hematopoiesis Myeloid progenitor cells |
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