m(6)A RNA methylation maintains hematopoietic stem cell identity and symmetric commitment Journal Article
| Authors: | Cheng, Y.; Luo, H.; Izzo, F.; Pickering, B. F.; Nguyen, D.; Myers, R.; Schurer, A.; Gourkanti, S.; Brüning, J. C.; Vu, L. P.; Jaffrey, S. R.; Landau, D. A.; Kharas, M. G. |
| Article Title: | m(6)A RNA methylation maintains hematopoietic stem cell identity and symmetric commitment |
| 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 m6A methyltransferase Mettl3 conditional knockout mice, we found that m6A-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. Cheng et al. uncover RNA methylation as a guardian in hematopoietic stem cell (HSC) fate decisions. m6A maintains hematopoietic stem cell symmetric commitment and identity. This study may provide a general mechanism for how RNA methylation controls cellular fate. © 2019 The Authors |
| Keywords: | controlled study; unclassified drug; nonhuman; animal cell; mouse; cell division; protein depletion; animal experiment; cell differentiation; cell population; transcriptomics; methyltransferase; messenger rna; myc protein; hematopoiesis; hematopoietic stem cell; catalysis; cell expansion; knockout mouse; myc; rna sequence; rna methylation; cell identity; male; female; priority journal; article; m6a; symmetric and asymmetric cell division; 6 n methyladenosine; mettl3 protein; single cell rna sequencing |
| Journal Title: | Cell Reports |
| Volume: | 28 |
| Issue: | 7 |
| ISSN: | 2211-1247 |
| Publisher: | Cell Press |
| Date Published: | 2019-08-13 |
| Start Page: | 1703 |
| End Page: | 1716.e6 |
| Language: | English |
| DOI: | 10.1016/j.celrep.2019.07.032 |
| PUBMED: | 31412241 |
| PROVIDER: | scopus |
| PMCID: | PMC6818972 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 1 November 2019 -- Source: Scopus |
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