Single-Cell Transcriptomic Analyses of Cell Fate Transitions during Human Cardiac Reprogramming
Direct cellular reprogramming provides a powerful platform to study cell plasticity and dissect mechanisms underlying cell fate determination. Here, we report a single-cell transcriptomic study of human cardiac (hiCM) reprogramming that utilizes an analysis pipeline incorporating current data normal...
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| Published in: | Cell stem cell Vol. 25; no. 1; p. 149 |
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| Main Authors: | , , , , , , , , , , , |
| Format: | Journal Article |
| Language: | English |
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United States
03.07.2019
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| ISSN: | 1875-9777, 1875-9777 |
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| Abstract | Direct cellular reprogramming provides a powerful platform to study cell plasticity and dissect mechanisms underlying cell fate determination. Here, we report a single-cell transcriptomic study of human cardiac (hiCM) reprogramming that utilizes an analysis pipeline incorporating current data normalization methods, multiple trajectory prediction algorithms, and a cell fate index calculation we developed to measure reprogramming progression. These analyses revealed hiCM reprogramming-specific features and a decision point at which cells either embark on reprogramming or regress toward their original fibroblast state. In combination with functional screening, we found that immune-response-associated DNA methylation is required for hiCM induction and validated several downstream targets of reprogramming factors as necessary for productive hiCM reprograming. Collectively, this single-cell transcriptomics study provides detailed datasets that reveal molecular features underlying hiCM determination and rigorous analytical pipelines for predicting cell fate conversion. |
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| AbstractList | Direct cellular reprogramming provides a powerful platform to study cell plasticity and dissect mechanisms underlying cell fate determination. Here, we report a single-cell transcriptomic study of human cardiac (hiCM) reprogramming that utilizes an analysis pipeline incorporating current data normalization methods, multiple trajectory prediction algorithms, and a cell fate index calculation we developed to measure reprogramming progression. These analyses revealed hiCM reprogramming-specific features and a decision point at which cells either embark on reprogramming or regress toward their original fibroblast state. In combination with functional screening, we found that immune-response-associated DNA methylation is required for hiCM induction and validated several downstream targets of reprogramming factors as necessary for productive hiCM reprograming. Collectively, this single-cell transcriptomics study provides detailed datasets that reveal molecular features underlying hiCM determination and rigorous analytical pipelines for predicting cell fate conversion. Direct cellular reprogramming provides a powerful platform to study cell plasticity and dissect mechanisms underlying cell fate determination. Here, we report a single-cell transcriptomic study of human cardiac (hiCM) reprogramming that utilizes an analysis pipeline incorporating current data normalization methods, multiple trajectory prediction algorithms, and a cell fate index calculation we developed to measure reprogramming progression. These analyses revealed hiCM reprogramming-specific features and a decision point at which cells either embark on reprogramming or regress toward their original fibroblast state. In combination with functional screening, we found that immune-response-associated DNA methylation is required for hiCM induction and validated several downstream targets of reprogramming factors as necessary for productive hiCM reprograming. Collectively, this single-cell transcriptomics study provides detailed datasets that reveal molecular features underlying hiCM determination and rigorous analytical pipelines for predicting cell fate conversion.Direct cellular reprogramming provides a powerful platform to study cell plasticity and dissect mechanisms underlying cell fate determination. Here, we report a single-cell transcriptomic study of human cardiac (hiCM) reprogramming that utilizes an analysis pipeline incorporating current data normalization methods, multiple trajectory prediction algorithms, and a cell fate index calculation we developed to measure reprogramming progression. These analyses revealed hiCM reprogramming-specific features and a decision point at which cells either embark on reprogramming or regress toward their original fibroblast state. In combination with functional screening, we found that immune-response-associated DNA methylation is required for hiCM induction and validated several downstream targets of reprogramming factors as necessary for productive hiCM reprograming. Collectively, this single-cell transcriptomics study provides detailed datasets that reveal molecular features underlying hiCM determination and rigorous analytical pipelines for predicting cell fate conversion. |
| Author | Qian, Li Liu, Jiandong Wang, Li Garbutt, Tiffany Zhou, Yang Gao, Xu Shen, Weining Welch, Joshua D Keepers, Benjamin Ma, Hong Prins, Jan F Liu, Ziqing |
| Author_xml | – sequence: 1 givenname: Yang surname: Zhou fullname: Zhou, Yang organization: Department of Pathology and Laboratory Medicine, University of North Carolina, Chapel Hill, Chapel Hill, NC 27599, USA; McAllister Heart Institute, University of North Carolina, Chapel Hill, Chapel Hill, NC 27599, USA – sequence: 2 givenname: Ziqing surname: Liu fullname: Liu, Ziqing organization: Department of Pathology and Laboratory Medicine, University of North Carolina, Chapel Hill, Chapel Hill, NC 27599, USA; McAllister Heart Institute, University of North Carolina, Chapel Hill, Chapel Hill, NC 27599, USA – sequence: 3 givenname: Joshua D surname: Welch fullname: Welch, Joshua D organization: Department of Computer Science, University of North Carolina, Chapel Hill, Chapel Hill, NC 27599, USA – sequence: 4 givenname: Xu surname: Gao fullname: Gao, Xu organization: Department of Statistics, University of California, Irvine, Irvine, CA 92697, USA – sequence: 5 givenname: Li surname: Wang fullname: Wang, Li organization: Department of Pathology and Laboratory Medicine, University of North Carolina, Chapel Hill, Chapel Hill, NC 27599, USA; McAllister Heart Institute, University of North Carolina, Chapel Hill, Chapel Hill, NC 27599, USA – sequence: 6 givenname: Tiffany surname: Garbutt fullname: Garbutt, Tiffany organization: Department of Pathology and Laboratory Medicine, University of North Carolina, Chapel Hill, Chapel Hill, NC 27599, USA; McAllister Heart Institute, University of North Carolina, Chapel Hill, Chapel Hill, NC 27599, USA – sequence: 7 givenname: Benjamin surname: Keepers fullname: Keepers, Benjamin organization: Department of Pathology and Laboratory Medicine, University of North Carolina, Chapel Hill, Chapel Hill, NC 27599, USA; McAllister Heart Institute, University of North Carolina, Chapel Hill, Chapel Hill, NC 27599, USA – sequence: 8 givenname: Hong surname: Ma fullname: Ma, Hong organization: Department of Pathology and Laboratory Medicine, University of North Carolina, Chapel Hill, Chapel Hill, NC 27599, USA; McAllister Heart Institute, University of North Carolina, Chapel Hill, Chapel Hill, NC 27599, USA – sequence: 9 givenname: Jan F surname: Prins fullname: Prins, Jan F organization: Department of Computer Science, University of North Carolina, Chapel Hill, Chapel Hill, NC 27599, USA – sequence: 10 givenname: Weining surname: Shen fullname: Shen, Weining organization: Department of Statistics, University of California, Irvine, Irvine, CA 92697, USA – sequence: 11 givenname: Jiandong surname: Liu fullname: Liu, Jiandong organization: Department of Pathology and Laboratory Medicine, University of North Carolina, Chapel Hill, Chapel Hill, NC 27599, USA; McAllister Heart Institute, University of North Carolina, Chapel Hill, Chapel Hill, NC 27599, USA – sequence: 12 givenname: Li surname: Qian fullname: Qian, Li email: li_qian@med.unc.edu organization: Department of Pathology and Laboratory Medicine, University of North Carolina, Chapel Hill, Chapel Hill, NC 27599, USA; McAllister Heart Institute, University of North Carolina, Chapel Hill, Chapel Hill, NC 27599, USA. Electronic address: li_qian@med.unc.edu |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/31230860$$D View this record in MEDLINE/PubMed |
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| SubjectTerms | Animals Cell Differentiation Cell Lineage Cellular Reprogramming Cellular Reprogramming Techniques Fibroblasts - physiology Humans Myocytes, Cardiac - physiology Sequence Analysis, RNA Single-Cell Analysis - methods Transcriptome |
| Title | Single-Cell Transcriptomic Analyses of Cell Fate Transitions during Human Cardiac Reprogramming |
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