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Single-cell architecture and functional requirement of alternative splicing during hematopoietic stem cell formation
Single-cell transcriptional profiling has rapidly advanced our understanding of the embryonic hematopoiesis; however, whether and what role RNA alternative splicing (AS) plays remains an enigma. This is important for understanding the mechanisms underlying splicing-associated hematopoietic diseases...
Autores principales: | , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Association for the Advancement of Science
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8741192/ https://www.ncbi.nlm.nih.gov/pubmed/34995116 http://dx.doi.org/10.1126/sciadv.abg5369 |
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author | Wang, Fang Tan, Puwen Zhang, Pengcheng Ren, Yue Zhou, Jie Li, Yunqiao Hou, Siyuan Li, Shuaili Zhang, Linlin Ma, Yanni Wang, Chaojie Tang, Wanbo Wang, Xiaoshuang Huo, Yue Hu, Yongfei Cui, Tianyu Niu, Chao Wang, Dong Liu, Bing Lan, Yu Yu, Jia |
author_facet | Wang, Fang Tan, Puwen Zhang, Pengcheng Ren, Yue Zhou, Jie Li, Yunqiao Hou, Siyuan Li, Shuaili Zhang, Linlin Ma, Yanni Wang, Chaojie Tang, Wanbo Wang, Xiaoshuang Huo, Yue Hu, Yongfei Cui, Tianyu Niu, Chao Wang, Dong Liu, Bing Lan, Yu Yu, Jia |
author_sort | Wang, Fang |
collection | PubMed |
description | Single-cell transcriptional profiling has rapidly advanced our understanding of the embryonic hematopoiesis; however, whether and what role RNA alternative splicing (AS) plays remains an enigma. This is important for understanding the mechanisms underlying splicing-associated hematopoietic diseases and for the derivation of therapeutic stem cells. Here, we used single-cell full-length transcriptome data to construct an isoform-based transcriptional atlas of the murine endothelial-to-hematopoietic stem cell (HSC) transition, which enables the identification of hemogenic signature isoforms and stage-specific AS events. We showed that the inclusion of these hemogenic-specific AS events was essential for hemogenic function in vitro. Expression data and knockout mouse studies highlighted the critical role of Srsf2: Early Srsf2 deficiency from endothelial cells affected the splicing pattern of several master hematopoietic regulators and significantly impaired HSC generation. These results redefine our understanding of the dynamic HSC developmental transcriptome and demonstrate that elaborately controlled RNA splicing governs cell fate in HSC formation. |
format | Online Article Text |
id | pubmed-8741192 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | American Association for the Advancement of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-87411922022-01-20 Single-cell architecture and functional requirement of alternative splicing during hematopoietic stem cell formation Wang, Fang Tan, Puwen Zhang, Pengcheng Ren, Yue Zhou, Jie Li, Yunqiao Hou, Siyuan Li, Shuaili Zhang, Linlin Ma, Yanni Wang, Chaojie Tang, Wanbo Wang, Xiaoshuang Huo, Yue Hu, Yongfei Cui, Tianyu Niu, Chao Wang, Dong Liu, Bing Lan, Yu Yu, Jia Sci Adv Biomedicine and Life Sciences Single-cell transcriptional profiling has rapidly advanced our understanding of the embryonic hematopoiesis; however, whether and what role RNA alternative splicing (AS) plays remains an enigma. This is important for understanding the mechanisms underlying splicing-associated hematopoietic diseases and for the derivation of therapeutic stem cells. Here, we used single-cell full-length transcriptome data to construct an isoform-based transcriptional atlas of the murine endothelial-to-hematopoietic stem cell (HSC) transition, which enables the identification of hemogenic signature isoforms and stage-specific AS events. We showed that the inclusion of these hemogenic-specific AS events was essential for hemogenic function in vitro. Expression data and knockout mouse studies highlighted the critical role of Srsf2: Early Srsf2 deficiency from endothelial cells affected the splicing pattern of several master hematopoietic regulators and significantly impaired HSC generation. These results redefine our understanding of the dynamic HSC developmental transcriptome and demonstrate that elaborately controlled RNA splicing governs cell fate in HSC formation. American Association for the Advancement of Science 2022-01-07 /pmc/articles/PMC8741192/ /pubmed/34995116 http://dx.doi.org/10.1126/sciadv.abg5369 Text en Copyright © 2022 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). https://creativecommons.org/licenses/by-nc/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial license (https://creativecommons.org/licenses/by-nc/4.0/) , which permits use, distribution, and reproduction in any medium, so long as the resultant use is not for commercial advantage and provided the original work is properly cited. |
spellingShingle | Biomedicine and Life Sciences Wang, Fang Tan, Puwen Zhang, Pengcheng Ren, Yue Zhou, Jie Li, Yunqiao Hou, Siyuan Li, Shuaili Zhang, Linlin Ma, Yanni Wang, Chaojie Tang, Wanbo Wang, Xiaoshuang Huo, Yue Hu, Yongfei Cui, Tianyu Niu, Chao Wang, Dong Liu, Bing Lan, Yu Yu, Jia Single-cell architecture and functional requirement of alternative splicing during hematopoietic stem cell formation |
title | Single-cell architecture and functional requirement of alternative splicing during hematopoietic stem cell formation |
title_full | Single-cell architecture and functional requirement of alternative splicing during hematopoietic stem cell formation |
title_fullStr | Single-cell architecture and functional requirement of alternative splicing during hematopoietic stem cell formation |
title_full_unstemmed | Single-cell architecture and functional requirement of alternative splicing during hematopoietic stem cell formation |
title_short | Single-cell architecture and functional requirement of alternative splicing during hematopoietic stem cell formation |
title_sort | single-cell architecture and functional requirement of alternative splicing during hematopoietic stem cell formation |
topic | Biomedicine and Life Sciences |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8741192/ https://www.ncbi.nlm.nih.gov/pubmed/34995116 http://dx.doi.org/10.1126/sciadv.abg5369 |
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