1. Department of clinical laboratory, The Second Affiliated Hospital, Zhejiang University School of Medicine, No. 88 Jiefang Road, Hangzhou, 310009, Zhejiang, China.
2. Department of Hematological Malignancies Translational Science, Gehr Family Center for Leukemia Research, Hematologic Malignancies and Stem Cell Transplantation Institute, Beckman Research Institute, City of Hope Medical Center, Duarte, CA 91010.
3. Department of Science and Development, The Second Affiliated Hospital, Zhejiang University School of Medicine, No. 88 Jiefang Road, Hangzhou, 310009, Zhejiang, China.
4. Department of Hematology, The Second Affiliated Hospital, Zhejiang University School of Medicine, No. 88 Jiefang Road, Hangzhou, 310009, Zhejiang, China.
*These authors contributed equally to this work.
Protein arginine methyltransferase 1 (PRMT1) is the predominant asymmetric (type I) methyltransferase in mammalian cells. Mounting evidence suggested that PRMT1 is essential to embryonic development and tumor pathogenesis, but its role in normal adult hematopoiesis is less studied. We used a Prmt1 conditional knockout (KO) mouse model to identify the role of PRMT1 in normal adult hematopoiesis. The results indicated that deletion of PRMT1 results in anemia and leukopenia, reducing terminal erythroid and lymphocyte differentiation. Additionally, we found a significant decrease of megakaryocyte progenitors (MkPs) compared with similarly treated littermate control mice. The frequency of short-term hematopoietic stem cells (ST-HSCs) and granulocyte-macrophage progenitors (GMPs) populations were significantly lower in PRMT1f/f/Mx1-CRE bone marrow (BM) compared with littermate control mice. Importantly, in-vitro replating assays and BM transplantation results revealed that PRMT1 KO results in reduced hematopoietic stem and progenitor cells (HSPCs) self-renewal capacity. Thus, we conclude that PRMT1 is required for hematopoietic differentiation and the competitive fitness of HSPCs, and we believed that PRMT1 serves as a key epigenetic regulator of normal hematopoiesis that occurs throughout life.
Keywords: PTMT1, HSPCs, normal hematopoiesis