A transcription factor atlas of directed differentiation
Transcription factors (TFs) regulate gene programs, thereby controlling diverse cellular processes and cell states. To comprehensively understand TFs and the programs they control, we created a barcoded library of all annotated human TF splice isoforms (>3,500) and applied it to build a TF Atlas...
| Main Authors: | , , , , , , , , , , , , , , , , , |
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| Other Authors: | |
| Format: | Article |
| Language: | English |
| Published: |
Elsevier BV
2023
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| Online Access: | https://hdl.handle.net/1721.1/150445 |
| _version_ | 1826190907689402368 |
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| author | Joung, Julia Ma, Sai Tay, Tristan Geiger-Schuller, Kathryn R Kirchgatterer, Paul C Verdine, Vanessa K Guo, Baolin Arias-Garcia, Mario A Allen, William E Singh, Ankita Kuksenko, Olena Abudayyeh, Omar O Gootenberg, Jonathan S Fu, Zhanyan Macrae, Rhiannon K Buenrostro, Jason D Regev, Aviv Zhang, Feng |
| author2 | Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences |
| author_facet | Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences Joung, Julia Ma, Sai Tay, Tristan Geiger-Schuller, Kathryn R Kirchgatterer, Paul C Verdine, Vanessa K Guo, Baolin Arias-Garcia, Mario A Allen, William E Singh, Ankita Kuksenko, Olena Abudayyeh, Omar O Gootenberg, Jonathan S Fu, Zhanyan Macrae, Rhiannon K Buenrostro, Jason D Regev, Aviv Zhang, Feng |
| author_sort | Joung, Julia |
| collection | MIT |
| description | Transcription factors (TFs) regulate gene programs, thereby controlling diverse cellular processes and cell states. To comprehensively understand TFs and the programs they control, we created a barcoded library of all annotated human TF splice isoforms (>3,500) and applied it to build a TF Atlas charting expression profiles of human embryonic stem cells (hESCs) overexpressing each TF at single-cell resolution. We mapped TF-induced expression profiles to reference cell types and validated candidate TFs for generation of diverse cell types, spanning all three germ layers and trophoblasts. Targeted screens with subsets of the library allowed us to create a tailored cellular disease model and integrate mRNA expression and chromatin accessibility data to identify downstream regulators. Finally, we characterized the effects of combinatorial TF overexpression by developing and validating a strategy for predicting combinations of TFs that produce target expression profiles matching reference cell types to accelerate cellular engineering efforts. |
| first_indexed | 2024-09-23T08:47:28Z |
| format | Article |
| id | mit-1721.1/150445 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T08:47:28Z |
| publishDate | 2023 |
| publisher | Elsevier BV |
| record_format | dspace |
| spelling | mit-1721.1/1504452023-04-07T03:50:26Z A transcription factor atlas of directed differentiation Joung, Julia Ma, Sai Tay, Tristan Geiger-Schuller, Kathryn R Kirchgatterer, Paul C Verdine, Vanessa K Guo, Baolin Arias-Garcia, Mario A Allen, William E Singh, Ankita Kuksenko, Olena Abudayyeh, Omar O Gootenberg, Jonathan S Fu, Zhanyan Macrae, Rhiannon K Buenrostro, Jason D Regev, Aviv Zhang, Feng Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences Transcription factors (TFs) regulate gene programs, thereby controlling diverse cellular processes and cell states. To comprehensively understand TFs and the programs they control, we created a barcoded library of all annotated human TF splice isoforms (>3,500) and applied it to build a TF Atlas charting expression profiles of human embryonic stem cells (hESCs) overexpressing each TF at single-cell resolution. We mapped TF-induced expression profiles to reference cell types and validated candidate TFs for generation of diverse cell types, spanning all three germ layers and trophoblasts. Targeted screens with subsets of the library allowed us to create a tailored cellular disease model and integrate mRNA expression and chromatin accessibility data to identify downstream regulators. Finally, we characterized the effects of combinatorial TF overexpression by developing and validating a strategy for predicting combinations of TFs that produce target expression profiles matching reference cell types to accelerate cellular engineering efforts. 2023-04-06T18:13:38Z 2023-04-06T18:13:38Z 2023-01 2023-04-06T18:11:01Z Article http://purl.org/eprint/type/JournalArticle https://hdl.handle.net/1721.1/150445 Joung, Julia, Ma, Sai, Tay, Tristan, Geiger-Schuller, Kathryn R, Kirchgatterer, Paul C et al. 2023. "A transcription factor atlas of directed differentiation." Cell, 186 (1). en 10.1016/j.cell.2022.11.026 Cell Creative Commons Attribution http://creativecommons.org/licenses/by/4.0/ application/pdf Elsevier BV Elsevier |
| spellingShingle | Joung, Julia Ma, Sai Tay, Tristan Geiger-Schuller, Kathryn R Kirchgatterer, Paul C Verdine, Vanessa K Guo, Baolin Arias-Garcia, Mario A Allen, William E Singh, Ankita Kuksenko, Olena Abudayyeh, Omar O Gootenberg, Jonathan S Fu, Zhanyan Macrae, Rhiannon K Buenrostro, Jason D Regev, Aviv Zhang, Feng A transcription factor atlas of directed differentiation |
| title | A transcription factor atlas of directed differentiation |
| title_full | A transcription factor atlas of directed differentiation |
| title_fullStr | A transcription factor atlas of directed differentiation |
| title_full_unstemmed | A transcription factor atlas of directed differentiation |
| title_short | A transcription factor atlas of directed differentiation |
| title_sort | transcription factor atlas of directed differentiation |
| url | https://hdl.handle.net/1721.1/150445 |
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