Diversification of reprogramming trajectories revealed by parallel single-cell transcriptome and chromatin accessibility sequencing
Cellular reprogramming suffers from low efficiency especially for the human cells. To deconstruct the heterogeneity and unravel the mechanisms for successful reprogramming, we adopted single-cell RNA sequencing (scRNA-Seq) and single-cell assay for transposase-accessible chromatin (scATAC-Seq) to pr...
| Main Authors: | , , , , , , , , , , , , , , |
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| Other Authors: | |
| Format: | Journal Article |
| Language: | English |
| Published: |
2020
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| Subjects: | |
| Online Access: | https://hdl.handle.net/10356/145388 |
| _version_ | 1811686937499533312 |
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| author | Xing, Qiao Rui El Farran, C. A. Gautam, P. Chuah, Y. S. Warrier, T. Toh, C. X. D. Kang, N. Y. Sugii, S. Chang, Y. T. Xu, J. Collins, J. J. Daley, G. Q. Li, H. Zhang, Li-Feng Loh, Y. H. |
| author2 | School of Biological Sciences |
| author_facet | School of Biological Sciences Xing, Qiao Rui El Farran, C. A. Gautam, P. Chuah, Y. S. Warrier, T. Toh, C. X. D. Kang, N. Y. Sugii, S. Chang, Y. T. Xu, J. Collins, J. J. Daley, G. Q. Li, H. Zhang, Li-Feng Loh, Y. H. |
| author_sort | Xing, Qiao Rui |
| collection | NTU |
| description | Cellular reprogramming suffers from low efficiency especially for the human cells. To deconstruct the heterogeneity and unravel the mechanisms for successful reprogramming, we adopted single-cell RNA sequencing (scRNA-Seq) and single-cell assay for transposase-accessible chromatin (scATAC-Seq) to profile reprogramming cells across various time points. Our analysis revealed that reprogramming cells proceed in an asynchronous trajectory and diversify into heterogeneous subpopulations. We identified fluorescent probes and surface markers to enrich for the early reprogrammed human cells. Furthermore, combinatory usage of the surface markers enabled the fine segregation of the early-intermediate cells with diverse reprogramming propensities. scATAC-Seq analysis further uncovered the genomic partitions and transcription factors responsible for the regulatory phasing of reprogramming process. Binary choice between a FOSL1 and a TEAD4-centric regulatory network determines the outcome of a successful reprogramming. Together, our study illuminates the multitude of diverse routes transversed by individual reprogramming cells and presents an integrative roadmap for identifying the mechanistic part list of the reprogramming machinery. |
| first_indexed | 2024-10-01T05:08:21Z |
| format | Journal Article |
| id | ntu-10356/145388 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2024-10-01T05:08:21Z |
| publishDate | 2020 |
| record_format | dspace |
| spelling | ntu-10356/1453882023-02-28T16:57:23Z Diversification of reprogramming trajectories revealed by parallel single-cell transcriptome and chromatin accessibility sequencing Xing, Qiao Rui El Farran, C. A. Gautam, P. Chuah, Y. S. Warrier, T. Toh, C. X. D. Kang, N. Y. Sugii, S. Chang, Y. T. Xu, J. Collins, J. J. Daley, G. Q. Li, H. Zhang, Li-Feng Loh, Y. H. School of Biological Sciences Science::Biological sciences Chromosomes Machinery Cellular reprogramming suffers from low efficiency especially for the human cells. To deconstruct the heterogeneity and unravel the mechanisms for successful reprogramming, we adopted single-cell RNA sequencing (scRNA-Seq) and single-cell assay for transposase-accessible chromatin (scATAC-Seq) to profile reprogramming cells across various time points. Our analysis revealed that reprogramming cells proceed in an asynchronous trajectory and diversify into heterogeneous subpopulations. We identified fluorescent probes and surface markers to enrich for the early reprogrammed human cells. Furthermore, combinatory usage of the surface markers enabled the fine segregation of the early-intermediate cells with diverse reprogramming propensities. scATAC-Seq analysis further uncovered the genomic partitions and transcription factors responsible for the regulatory phasing of reprogramming process. Binary choice between a FOSL1 and a TEAD4-centric regulatory network determines the outcome of a successful reprogramming. Together, our study illuminates the multitude of diverse routes transversed by individual reprogramming cells and presents an integrative roadmap for identifying the mechanistic part list of the reprogramming machinery. Agency for Science, Technology and Research (A*STAR) Ministry of Education (MOE) Ministry of Health (MOH) National Medical Research Council (NMRC) National Research Foundation (NRF) Published version H.L. is supported by the NIH (AG056318, AG61796, and CA208517), the Glenn Foundation for Medical Research, Mayo Clinic Center for Biomedical Discovery, Center for Individualized Medicine, Mayo Clinic Cancer Center, and the David F. and Margaret T. Grohne Cancer Immunology and Immunotherapy Program. L.F.Z. is supported by the Singapore Ministry of Education Academic Research Fund (MOE2015-T2-1-093) and Singapore National Research Foundation under its Cooperative Basic Research Grant administered by the Singapore Ministry of Health’s National Medical Research Council (NMRC/CBRG/0092/2015). N.Y.K. and Y.T.C. are supported by the JCO Development Programme Grant (1334k00083). Y.H.L. is supported by the NRF Investigatorship award (NRFI2018-02 grant), JCO Development Programme Grant (1534n00153 and 1334k00083), and the Singapore National Research Foundation under its Cooperative Basic Research Grant administered by the Singapore Ministry of Health’s National Medical Research Council (NMRC/CBRG/0092/2015). We are grateful to the Biomedical Research Council, Agency for Science, Technology and Research, Singapore for research funding. 2020-12-21T02:20:45Z 2020-12-21T02:20:45Z 2020 Journal Article Xing, Q. R., El Farran, C. A., Gautam, P., Chuah, Y. S., Warrier, T., Toh, C. X. D., . . . Loh, Y. H. (2020). Diversification of reprogramming trajectories revealed by parallel single-cell transcriptome and chromatin accessibility sequencing. Science Advances, 6(37), eaba1190-. doi:10.1126/sciadv.aba1190 2375-2548 https://hdl.handle.net/10356/145388 10.1126/sciadv.aba1190 32917699 37 6 en MOE2015-T2-1-093 NMRC/CBRG/0092/2015 NRFI2018-02 Science Advances © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC). application/pdf |
| spellingShingle | Science::Biological sciences Chromosomes Machinery Xing, Qiao Rui El Farran, C. A. Gautam, P. Chuah, Y. S. Warrier, T. Toh, C. X. D. Kang, N. Y. Sugii, S. Chang, Y. T. Xu, J. Collins, J. J. Daley, G. Q. Li, H. Zhang, Li-Feng Loh, Y. H. Diversification of reprogramming trajectories revealed by parallel single-cell transcriptome and chromatin accessibility sequencing |
| title | Diversification of reprogramming trajectories revealed by parallel single-cell transcriptome and chromatin accessibility sequencing |
| title_full | Diversification of reprogramming trajectories revealed by parallel single-cell transcriptome and chromatin accessibility sequencing |
| title_fullStr | Diversification of reprogramming trajectories revealed by parallel single-cell transcriptome and chromatin accessibility sequencing |
| title_full_unstemmed | Diversification of reprogramming trajectories revealed by parallel single-cell transcriptome and chromatin accessibility sequencing |
| title_short | Diversification of reprogramming trajectories revealed by parallel single-cell transcriptome and chromatin accessibility sequencing |
| title_sort | diversification of reprogramming trajectories revealed by parallel single cell transcriptome and chromatin accessibility sequencing |
| topic | Science::Biological sciences Chromosomes Machinery |
| url | https://hdl.handle.net/10356/145388 |
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