The mRNA m(6)A reader YTHDF2 suppresses proinflammatory pathways and sustains hematopoietic stem cell function
DC Field | Value | Language |
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dc.contributor.author | Mapperley, Christopher | - |
dc.contributor.author | van de Lagemaat, Louie N. | - |
dc.contributor.author | Lawson, Hannah | - |
dc.contributor.author | Tavosanis, Andrea | - |
dc.contributor.author | Paris, Jasmin | - |
dc.contributor.author | Campos, Joana | - |
dc.contributor.author | Wotherspoon, David | - |
dc.contributor.author | Durko, Jozef | - |
dc.contributor.author | Sarapuu, Annika | - |
dc.contributor.author | Choe, Junho | - |
dc.contributor.author | Ivanova, Ivayla | - |
dc.contributor.author | Krause, Daniela S. | - |
dc.contributor.author | von Kriegsheim, Alex | - |
dc.contributor.author | Much, Christian | - |
dc.contributor.author | Morgan, Marcos | - |
dc.contributor.author | Gregory, Richard I. | - |
dc.contributor.author | Mead, Adam J. | - |
dc.contributor.author | O'Carroll, Donal | - |
dc.contributor.author | Kranc, Kamil R. | - |
dc.date.accessioned | 2021-07-30T04:48:05Z | - |
dc.date.available | 2021-07-30T04:48:05Z | - |
dc.date.created | 2021-07-14 | - |
dc.date.issued | 2021-03 | - |
dc.identifier.issn | 0022-1007 | - |
dc.identifier.uri | https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/1317 | - |
dc.description.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. | - |
dc.language | 영어 | - |
dc.language.iso | en | - |
dc.publisher | ROCKEFELLER UNIV PRESS | - |
dc.title | The mRNA m(6)A reader YTHDF2 suppresses proinflammatory pathways and sustains hematopoietic stem cell function | - |
dc.type | Article | - |
dc.contributor.affiliatedAuthor | Choe, Junho | - |
dc.identifier.doi | 10.1084/jem.20200829 | - |
dc.identifier.scopusid | 2-s2.0-85095802769 | - |
dc.identifier.wosid | 000625357800004 | - |
dc.identifier.bibliographicCitation | JOURNAL OF EXPERIMENTAL MEDICINE, v.218, no.3, pp.1 - 11 | - |
dc.relation.isPartOf | JOURNAL OF EXPERIMENTAL MEDICINE | - |
dc.citation.title | JOURNAL OF EXPERIMENTAL MEDICINE | - |
dc.citation.volume | 218 | - |
dc.citation.number | 3 | - |
dc.citation.startPage | 1 | - |
dc.citation.endPage | 11 | - |
dc.type.rims | ART | - |
dc.type.docType | Article | - |
dc.description.journalClass | 1 | - |
dc.description.isOpenAccess | Y | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.relation.journalResearchArea | Immunology | - |
dc.relation.journalResearchArea | Research & Experimental Medicine | - |
dc.relation.journalWebOfScienceCategory | Immunology | - |
dc.relation.journalWebOfScienceCategory | Medicine, Research & Experimental | - |
dc.subject.keywordPlus | MYELOID DIFFERENTIATION | - |
dc.subject.keywordPlus | CHRONIC EXPOSURE | - |
dc.subject.keywordPlus | TRANSLATION | - |
dc.subject.keywordPlus | EXPRESSION | - |
dc.subject.keywordPlus | REGULATOR | - |
dc.subject.keywordPlus | PROLIFERATION | - |
dc.subject.keywordPlus | LEUKEMIA | - |
dc.identifier.url | https://rupress.org/jem/article/218/3/e20200829/211520/The-mRNA-m6A-reader-YTHDF2-suppresses | - |
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