Cheng, Yuanming, Luo, Hanzhi, Izzo, Franco, Pickering, Brian F., Myers, Robert, Schurer, Alexandra, Gourkanti, Saroj, Bruening, Jens C., Vu, Ly P., Jaffrey, Samie R., Landau, Dan A. and Kharas, Michael G. (2019). m(6)A RNA Methylation Maintains Hematopoietic Stem Cell Identity and Symmetric Commitment. Cell Reports, 28 (7). S. 1703 - 1723. CAMBRIDGE: CELL PRESS. ISSN 2211-1247

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Abstract

Stem cells balance cellular fates through asymmetric and symmetric divisions in order to self-renew or to generate downstream progenitors. Symmetric commitment divisions in stem cells are required for rapid regeneration during tissue damage and stress. The control of symmetric commitment remains poorly defined. Using single-cell RNA sequencing (scRNA-seq) in combination with transcriptomic profiling of HSPCs (hematopoietic stem and progenitor cells) from control and m(6)A methyltransferase Mettl3 conditional knockout mice, we found that m(6)A-deficient hematopoietic stem cells (HSCs) fail to symmetrically differentiate. Dividing HSCs are expanded and are blocked in an intermediate state that molecularly and functionally resembles multipotent progenitors. Mechanistically, RNA methylation controls Myc mRNA abundance in differentiating HSCs. We identified MYC as a marker for HSC asymmetric and symmetric commitment. Overall, our results indicate that RNA methylation controls symmetric commitment and cell identity of HSCs and may provide a general mechanism for how stem cells regulate differentiation fate choice.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Cheng, YuanmingUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Luo, HanzhiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Izzo, FrancoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pickering, Brian F.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Myers, RobertUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schurer, AlexandraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gourkanti, SarojUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bruening, Jens C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Vu, Ly P.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Jaffrey, Samie R.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Landau, Dan A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kharas, Michael G.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-144416
DOI: 10.1016/j.celrep.2019.07.032
Journal or Publication Title: Cell Reports
Volume: 28
Number: 7
Page Range: S. 1703 - 1723
Date: 2019
Publisher: CELL PRESS
Place of Publication: CAMBRIDGE
ISSN: 2211-1247
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
MYELOID-LEUKEMIA; PROGENITOR CELLS; TRANSLATION; DIVISION; FATE; DIFFERENTIATION; WRITERSMultiple languages
Cell BiologyMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/14441

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