m6A RNA Methylation Maintains Hematopoietic Stem Cell Identity and Symmetric Commitment
Summary: 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 re...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2019-08-01
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| Series: | Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124719309295 |
| _version_ | 1818657712522657792 |
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| author | Yuanming Cheng Hanzhi Luo Franco Izzo Brian F. Pickering Diu Nguyen Robert Myers Alexandra Schurer Saroj Gourkanti Jens C. Brüning Ly P. Vu Samie R. Jaffrey Dan A. Landau Michael G. Kharas |
| author_facet | Yuanming Cheng Hanzhi Luo Franco Izzo Brian F. Pickering Diu Nguyen Robert Myers Alexandra Schurer Saroj Gourkanti Jens C. Brüning Ly P. Vu Samie R. Jaffrey Dan A. Landau Michael G. Kharas |
| author_sort | Yuanming Cheng |
| collection | DOAJ |
| description | Summary: 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. Keywords: m6A, RNA methylation, hematopoietic stem cell, cell identity, symmetric and asymmetric cell division, MYC |
| first_indexed | 2024-12-17T03:45:50Z |
| format | Article |
| id | doaj.art-d0575c334f4841de919b97361dfd2bba |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-17T03:45:50Z |
| publishDate | 2019-08-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-d0575c334f4841de919b97361dfd2bba2022-12-21T22:04:53ZengElsevierCell Reports2211-12472019-08-0128717031716.e6m6A RNA Methylation Maintains Hematopoietic Stem Cell Identity and Symmetric CommitmentYuanming Cheng0Hanzhi Luo1Franco Izzo2Brian F. Pickering3Diu Nguyen4Robert Myers5Alexandra Schurer6Saroj Gourkanti7Jens C. Brüning8Ly P. Vu9Samie R. Jaffrey10Dan A. Landau11Michael G. Kharas12Molecular Pharmacology Program, Center for Cell Engineering, Center for Stem Cell Biology, Center for Experimental Therapeutics, Center for Hematologic Malignancies, Memorial Sloan Kettering Cancer Center, New York, NY, USAMolecular Pharmacology Program, Center for Cell Engineering, Center for Stem Cell Biology, Center for Experimental Therapeutics, Center for Hematologic Malignancies, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Molecular Biology and Biochemistry, Simon Fraser University, Vancouver, BC, CanadaNew York Genome Center, New York, NY, USA; Meyer Cancer Center, Weill Cornell Medicine, New York, NY, USA; Molecular Biology and Biochemistry, Simon Fraser University, Vancouver, BC, CanadaDepartment of Pharmacology, Weill Cornell Medicine, Cornell University, New York, NY, USAMolecular Pharmacology Program, Center for Cell Engineering, Center for Stem Cell Biology, Center for Experimental Therapeutics, Center for Hematologic Malignancies, Memorial Sloan Kettering Cancer Center, New York, NY, USANew York Genome Center, New York, NY, USA; Meyer Cancer Center, Weill Cornell Medicine, New York, NY, USAMolecular Pharmacology Program, Center for Cell Engineering, Center for Stem Cell Biology, Center for Experimental Therapeutics, Center for Hematologic Malignancies, Memorial Sloan Kettering Cancer Center, New York, NY, USAMolecular Pharmacology Program, Center for Cell Engineering, Center for Stem Cell Biology, Center for Experimental Therapeutics, Center for Hematologic Malignancies, Memorial Sloan Kettering Cancer Center, New York, NY, USADepartment of Mouse Genetics and Metabolism, Institute for Genetics and Center for Molecular Medicine (CMMC), University of Cologne, Zülpicher Strasse 47b, 50674 Cologne, GermanyMolecular Pharmacology Program, Center for Cell Engineering, Center for Stem Cell Biology, Center for Experimental Therapeutics, Center for Hematologic Malignancies, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Terry Fox Laboratory, British Columbia Cancer Research Centre, Vancouver, BC, Canada; Molecular Biology and Biochemistry, Simon Fraser University, Vancouver, BC, CanadaDepartment of Pharmacology, Weill Cornell Medicine, Cornell University, New York, NY, USANew York Genome Center, New York, NY, USA; Meyer Cancer Center, Weill Cornell Medicine, New York, NY, USA; Institute of Computational Biomedicine, Weill Cornell Medicine, New York, NY, USA; Corresponding authorMolecular Pharmacology Program, Center for Cell Engineering, Center for Stem Cell Biology, Center for Experimental Therapeutics, Center for Hematologic Malignancies, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Corresponding authorSummary: 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. Keywords: m6A, RNA methylation, hematopoietic stem cell, cell identity, symmetric and asymmetric cell division, MYChttp://www.sciencedirect.com/science/article/pii/S2211124719309295 |
| spellingShingle | Yuanming Cheng Hanzhi Luo Franco Izzo Brian F. Pickering Diu Nguyen Robert Myers Alexandra Schurer Saroj Gourkanti Jens C. Brüning Ly P. Vu Samie R. Jaffrey Dan A. Landau Michael G. Kharas m6A RNA Methylation Maintains Hematopoietic Stem Cell Identity and Symmetric Commitment Cell Reports |
| title | m6A RNA Methylation Maintains Hematopoietic Stem Cell Identity and Symmetric Commitment |
| title_full | m6A RNA Methylation Maintains Hematopoietic Stem Cell Identity and Symmetric Commitment |
| title_fullStr | m6A RNA Methylation Maintains Hematopoietic Stem Cell Identity and Symmetric Commitment |
| title_full_unstemmed | m6A RNA Methylation Maintains Hematopoietic Stem Cell Identity and Symmetric Commitment |
| title_short | m6A RNA Methylation Maintains Hematopoietic Stem Cell Identity and Symmetric Commitment |
| title_sort | m6a rna methylation maintains hematopoietic stem cell identity and symmetric commitment |
| url | http://www.sciencedirect.com/science/article/pii/S2211124719309295 |
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