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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| Format: | Article |
| Language: | English |
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American Association for the Advancement of Science (AAAS)
2021
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| Online Access: | https://hdl.handle.net/1721.1/133493 |
| _version_ | 1811087736279400448 |
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| author | Xing, QR El Farran, CA Gautam, P Chuah, YS Warrier, T Toh, CXD Kang, NY Sugii, S Chang, YT Xu, J Collins, JJ Daley, GQ Li, H Zhang, LF Loh, YH |
| author2 | Massachusetts Institute of Technology. Institute for Medical Engineering & Science |
| author_facet | Massachusetts Institute of Technology. Institute for Medical Engineering & Science Xing, QR El Farran, CA Gautam, P Chuah, YS Warrier, T Toh, CXD Kang, NY Sugii, S Chang, YT Xu, J Collins, JJ Daley, GQ Li, H Zhang, LF Loh, YH |
| author_sort | Xing, QR |
| collection | MIT |
| 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 | 2024-09-23T13:51:12Z |
| format | Article |
| id | mit-1721.1/133493 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T13:51:12Z |
| publishDate | 2021 |
| publisher | American Association for the Advancement of Science (AAAS) |
| record_format | dspace |
| spelling | mit-1721.1/1334932024-03-20T19:17:25Z Diversification of reprogramming trajectories revealed by parallel single-cell transcriptome and chromatin accessibility sequencing Xing, QR El Farran, CA Gautam, P Chuah, YS Warrier, T Toh, CXD Kang, NY Sugii, S Chang, YT Xu, J Collins, JJ Daley, GQ Li, H Zhang, LF Loh, YH Massachusetts Institute of Technology. Institute for Medical Engineering & Science Massachusetts Institute of Technology. Department of Biological Engineering Massachusetts Institute of Technology. Synthetic Biology Center 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. 2021-10-27T19:53:09Z 2021-10-27T19:53:09Z 2020 2021-08-25T18:15:03Z Article http://purl.org/eprint/type/JournalArticle https://hdl.handle.net/1721.1/133493 en 10.1126/SCIADV.ABA1190 Science Advances Creative Commons Attribution NonCommercial License 4.0 https://creativecommons.org/licenses/by-nc/4.0/ application/pdf American Association for the Advancement of Science (AAAS) Science Advances |
| spellingShingle | Xing, QR El Farran, CA Gautam, P Chuah, YS Warrier, T Toh, CXD Kang, NY Sugii, S Chang, YT Xu, J Collins, JJ Daley, GQ Li, H Zhang, LF Loh, YH 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 |
| url | https://hdl.handle.net/1721.1/133493 |
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