{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Okuyama K"],"funding":["NEI NIH HHS","Telethon","NIDDK NIH HHS","NCI NIH HHS"],"pagination":["13410-5"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC3746909"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["110(33)"],"pubmed_abstract":["Lineage specification is thought to be largely regulated at the level of transcription, where lineage-specific transcription factors drive specific cell fates. MicroRNAs (miR), vital to many cell functions, act posttranscriptionally to decrease the expression of target mRNAs. MLL-AF4 acute lymphocytic leukemia exhibits both myeloid and B-cell surface markers, suggesting that the transformed cells are B-cell myeloid progenitor cells. Through gain- and loss-of-function experiments, we demonstrated that microRNA 126 (miR-126) drives B-cell myeloid biphenotypic leukemia differentiation toward B cells without changing expression of E2A immunoglobulin enhancer-binding factor E12/E47 (E2A), early B-cell factor 1 (EBF1), or paired box protein 5, which are critical transcription factors in B-lymphopoiesis. Similar induction of B-cell differentiation by miR-126 was observed in normal hematopoietic cells in vitro and in vivo in uncommitted murine c-Kit(+)Sca1(+)Lineage(-) cells, with insulin regulatory subunit-1 acting as a target of miR-126. Importantly, in EBF1-deficient hematopoietic progenitor cells, which fail to differentiate into B cells, miR-126 significantly up-regulated B220, and induced the expression of B-cell genes, including recombination activating genes-1/2 and CD79a/b. These data suggest that miR-126 can at least partly rescue B-cell development independently of EBF1. These experiments show that miR-126 regulates myeloid vs. B-cell fate through an alternative machinery, establishing the critical role of miRNAs in the lineage specification of multipotent mammalian cells."],"journal":["Proceedings of the National Academy of Sciences of the United States of America"],"pubmed_title":["MicroRNA-126-mediated control of cell fate in B-cell myeloid progenitors as a potential alternative to transcriptional factors."],"pmcid":["PMC3746909"],"funding_grant_id":["R01 EY021862","P30 CA014051","R01 DK068348","TGT11S01"],"pubmed_authors":["Harnprasopwat R","Tojo A","Kotani A","Chanda B","Kawamoto H","Yokoyama K","Ando K","Hozumi K","Kawamata T","Lodish HF","Ikawa T","Wang S","Gentner B","Lu J","Toyoshima T","Okuyama K","Yamashita R","Ha D"],"additional_accession":[]},"is_claimable":false,"name":"MicroRNA-126-mediated control of cell fate in B-cell myeloid progenitors as a potential alternative to transcriptional factors.","description":"Lineage specification is thought to be largely regulated at the level of transcription, where lineage-specific transcription factors drive specific cell fates. MicroRNAs (miR), vital to many cell functions, act posttranscriptionally to decrease the expression of target mRNAs. MLL-AF4 acute lymphocytic leukemia exhibits both myeloid and B-cell surface markers, suggesting that the transformed cells are B-cell myeloid progenitor cells. Through gain- and loss-of-function experiments, we demonstrated that microRNA 126 (miR-126) drives B-cell myeloid biphenotypic leukemia differentiation toward B cells without changing expression of E2A immunoglobulin enhancer-binding factor E12/E47 (E2A), early B-cell factor 1 (EBF1), or paired box protein 5, which are critical transcription factors in B-lymphopoiesis. Similar induction of B-cell differentiation by miR-126 was observed in normal hematopoietic cells in vitro and in vivo in uncommitted murine c-Kit(+)Sca1(+)Lineage(-) cells, with insulin regulatory subunit-1 acting as a target of miR-126. Importantly, in EBF1-deficient hematopoietic progenitor cells, which fail to differentiate into B cells, miR-126 significantly up-regulated B220, and induced the expression of B-cell genes, including recombination activating genes-1/2 and CD79a/b. These data suggest that miR-126 can at least partly rescue B-cell development independently of EBF1. These experiments show that miR-126 regulates myeloid vs. B-cell fate through an alternative machinery, establishing the critical role of miRNAs in the lineage specification of multipotent mammalian cells.","dates":{"release":"2013-01-01T00:00:00Z","publication":"2013 Aug","modification":"2026-05-03T21:23:06.198Z","creation":"2026-04-07T19:42:04.085Z"},"accession":"S-EPMC3746909","cross_references":{"pubmed":["23893300"],"doi":["10.1073/pnas.1220710110"]}}