PMID- 34743190 OWN - NLM STAT- MEDLINE DCOM- 20220311 LR - 20220418 IS - 1476-5551 (Electronic) IS - 0887-6924 (Linking) VI - 36 IP - 3 DP - 2022 Mar TI - The GPI-anchored protein CD109 protects hematopoietic progenitor cells from undergoing erythroid differentiation induced by TGF-beta. PG - 847-855 LID - 10.1038/s41375-021-01463-3 [doi] AB - Although a glycosylphosphatidylinositol-anchored protein (GPI-AP) CD109 serves as a TGF-beta co-receptor and inhibits TGF-beta signaling in keratinocytes, the role of CD109 on hematopoietic stem progenitor cells (HSPCs) remains unknown. We studied the effect of CD109 knockout (KO) or knockdown (KD) on TF-1, a myeloid leukemia cell line that expresses CD109, and primary human HSPCs. CD109-KO or KD TF-1 cells underwent erythroid differentiation in the presence of TGF-beta. CD109 was more abundantly expressed in hematopoietic stem cells (HSCs) than in multipotent progenitors and HSPCs of human bone marrow (BM) and cord blood but was not detected in mouse HSCs. Erythroid differentiation was induced by TGF-beta to a greater extent in CD109-KD cord blood or iPS cell-derived megakaryocyte-erythrocyte progenitor cells (MEPs) than in wild-type MEPs. When we analyzed the phenotype of peripheral blood MEPs of patients with paroxysmal nocturnal hemoglobinuria who had both GPI(+) and GPI(-) CD34(+) cells, the CD36 expression was more evident in CD109(-) MEPs than CD109(+) MEPs. In summary, CD109 suppresses TGF-beta signaling in HSPCs, and the lack of CD109 may increase the sensitivity of PIGA-mutated HSPCs to TGF-beta, thus leading to the preferential commitment of erythroid progenitor cells to mature red blood cells in immune-mediated BM failure. CI - (c) 2021. The Author(s), under exclusive licence to Springer Nature Limited. FAU - Tanabe, Mikoto AU - Tanabe M AD - Department of Hematology, Faculty of Medicine, Institute of Medical Pharmaceutical and Health Sciences, Kanazawa University, Kanazawa, Japan. FAU - Hosokawa, Kohei AU - Hosokawa K AUID- ORCID: 0000-0002-3423-1523 AD - Department of Hematology, Faculty of Medicine, Institute of Medical Pharmaceutical and Health Sciences, Kanazawa University, Kanazawa, Japan. FAU - Nguyen, Mai Anh Thi AU - Nguyen MAT AD - Department of Hematology, Faculty of Medicine, Institute of Medical Pharmaceutical and Health Sciences, Kanazawa University, Kanazawa, Japan. AD - Pediatric Department, University of Medicine and Pharmacy at HCMC, Ho Chi Minh City, Vietnam. FAU - Nakagawa, Noriharu AU - Nakagawa N AD - Department of Hematology, Faculty of Medicine, Institute of Medical Pharmaceutical and Health Sciences, Kanazawa University, Kanazawa, Japan. FAU - Maruyama, Kana AU - Maruyama K AD - Department of Hematology, Faculty of Medicine, Institute of Medical Pharmaceutical and Health Sciences, Kanazawa University, Kanazawa, Japan. FAU - Tsuji, Noriaki AU - Tsuji N AD - Department of Hematology, Faculty of Medicine, Institute of Medical Pharmaceutical and Health Sciences, Kanazawa University, Kanazawa, Japan. FAU - Urushihara, Ryota AU - Urushihara R AD - Department of Hematology, Faculty of Medicine, Institute of Medical Pharmaceutical and Health Sciences, Kanazawa University, Kanazawa, Japan. FAU - Espinoza, Luis AU - Espinoza L AD - Department of Clinical Laboratory Sciences, Kanazawa University Graduate School, Kanazawa, Japan. FAU - Elbadry, Mahmoud I AU - Elbadry MI AUID- ORCID: 0000-0001-5487-9493 AD - Department of Internal Medicine, Division of Hematology, Faculty of Medicine, Sohag University, Sohag, Egypt. FAU - Mohiuddin, Md AU - Mohiuddin M AUID- ORCID: 0000-0002-7313-8655 AD - Department of Respiratory Medicine, Kanazawa University, Kanazawa, Japan. FAU - Katagiri, Takamasa AU - Katagiri T AD - Department of Clinical Laboratory Sciences, Kanazawa University Graduate School, Kanazawa, Japan. FAU - Ono, Masanori AU - Ono M AD - Department of Obstetrics and Gynecology, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Japan. FAU - Fujiwara, Hiroshi AU - Fujiwara H AD - Department of Obstetrics and Gynecology, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Japan. FAU - Chonabayashi, Kazuhisa AU - Chonabayashi K AD - Center for iPS Cell Research and Application, Kyoto University, Kyoto, Japan. AD - Department of Hematology and Oncology, Graduate School of Medicine, Kyoto University, Kyoto, Japan. FAU - Yoshida, Yoshinori AU - Yoshida Y AD - Center for iPS Cell Research and Application, Kyoto University, Kyoto, Japan. FAU - Yamazaki, Hirohito AU - Yamazaki H AUID- ORCID: 0000-0003-3018-2098 AD - Division of Transfusion Medicine, Kanazawa University Hospital, Kanazawa, Japan. FAU - Hirao, Atsushi AU - Hirao A AD - Division of Molecular Genetics, Cancer and Stem Cell Research Program, Cancer Research Institute, Kanazawa University, Kanazawa, Japan. AD - WPI Nano Life Science Institute, Kanazawa University, Kanazawa, Japan. FAU - Nakao, Shinji AU - Nakao S AUID- ORCID: 0000-0002-9674-624X AD - Department of Hematology, Faculty of Medicine, Institute of Medical Pharmaceutical and Health Sciences, Kanazawa University, Kanazawa, Japan. snakao8205@staff.kanazawa-u.ac.jp. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20211106 PL - England TA - Leukemia JT - Leukemia JID - 8704895 RN - 0 (Antigens, CD) RN - 0 (CD109 protein, human) RN - 0 (GPI-Linked Proteins) RN - 0 (Neoplasm Proteins) RN - 0 (Transforming Growth Factor beta) SB - IM MH - Antigens, CD/*metabolism MH - Cell Differentiation MH - Cell Line MH - Cells, Cultured MH - Erythroid Cells/*cytology/metabolism MH - Erythropoiesis MH - GPI-Linked Proteins/metabolism MH - Hematopoiesis MH - Hematopoietic Stem Cells/*cytology/metabolism MH - Humans MH - Neoplasm Proteins/*metabolism MH - Transforming Growth Factor beta/*metabolism EDAT- 2021/11/08 06:00 MHDA- 2022/03/12 06:00 CRDT- 2021/11/07 20:45 PHST- 2021/03/15 00:00 [received] PHST- 2021/10/21 00:00 [accepted] PHST- 2021/10/09 00:00 [revised] PHST- 2021/11/08 06:00 [pubmed] PHST- 2022/03/12 06:00 [medline] PHST- 2021/11/07 20:45 [entrez] AID - 10.1038/s41375-021-01463-3 [pii] AID - 10.1038/s41375-021-01463-3 [doi] PST - ppublish SO - Leukemia. 2022 Mar;36(3):847-855. doi: 10.1038/s41375-021-01463-3. Epub 2021 Nov 6.