The mRNA m(6)A reader YTHDF2 suppresses proinflammatory pathways and sustains hematopoietic stem cell function
- Title
- The mRNA m(6)A reader YTHDF2 suppresses proinflammatory pathways and sustains hematopoietic stem cell function
- Author
- 최준호
- Issue Date
- 2021-03
- Publisher
- ROCKEFELLER UNIV PRESS
- Citation
- JOURNAL OF EXPERIMENTAL MEDICINE, v. 218, NO. 3, article no. e20200829, Page. 1-11
- Abstract
- The mRNA N-6-methyladenosine (m(6)A) modification has emerged as an essential regulator of normal and malignant hematopoiesis. Inactivation of the m(6)A mRNA reader YTHDF2, which recognizes m(6)A-modified transcripts to promote m(6)A-mRNA degradation, results in hematopoietic stem cell (HSC) expansion and compromises acute myeloid leukemia. Here we investigate the long-term impact of YTHDF2 deletion on HSC maintenance and multilineage hematopoiesis. We demonstrate that Ythdf2-deficient HSCs from young mice fail upon serial transplantation, display increased abundance of multiple m(6)A-modified inflammation-related transcripts, and chronically activate proinflammatory pathways. Consistent with the detrimental consequences of chronic activation of inflammatory pathways in HSCs, hematopoiesis-specific Ythdf2 deficiency results in a progressive myeloid bias, loss of lymphoid potential, HSC expansion, and failure of aged Ythdf2-deficient HSCs to reconstitute multilineage hematopoiesis. Experimentally induced inflammation increases YTHDF2 expression, and YTHDF2 is required to protect HSCs from this insult. Thus, our study positions YTHDF2 as a repressor of inflammatory pathways in HSCs and highlights the significance of m(6)A in long-term HSC maintenance.
- URI
- https://rupress.org/jem/article/218/3/e20200829/211520/The-mRNA-m6A-reader-YTHDF2-suppresseshttps://repository.hanyang.ac.kr/handle/20.500.11754/177934
- ISSN
- 0022-1007;1540-9538
- DOI
- 10.1084/jem.20200829
- Appears in Collections:
- COLLEGE OF NATURAL SCIENCES[S](자연과학대학) > LIFE SCIENCE(생명과학과) > Articles
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