An Optogenetic‐Controlled Cell Reprogramming System for Driving Cell Fate and Light‐Responsive Chimeric Mice
Abstract Pluripotent stem cells (PSCs) hold great promise for cell‐based therapies, disease modeling, and drug discovery. Classic somatic cell reprogramming to generate induced pluripotent stem cells (iPSCs) is often achieved based on overexpression of transcription factors (TFs). However, this proc...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Wiley
2023-02-01
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| Series: | Advanced Science |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/advs.202202858 |
| _version_ | 1797688117366358016 |
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| author | Meiyan Wang Yuanxiao Liu Ziwei Wang Longliang Qiao Xiaoding Ma Lingfeng Hu Deqiang Kong Yuan Wang Haifeng Ye |
| author_facet | Meiyan Wang Yuanxiao Liu Ziwei Wang Longliang Qiao Xiaoding Ma Lingfeng Hu Deqiang Kong Yuan Wang Haifeng Ye |
| author_sort | Meiyan Wang |
| collection | DOAJ |
| description | Abstract Pluripotent stem cells (PSCs) hold great promise for cell‐based therapies, disease modeling, and drug discovery. Classic somatic cell reprogramming to generate induced pluripotent stem cells (iPSCs) is often achieved based on overexpression of transcription factors (TFs). However, this process is limited by side effect of overexpressed TFs and unpredicted targeting of TFs. Pinpoint control over endogenous TFs expression can provide the ability to reprogram cell fate and tissue function. Here, a light‐inducible cell reprogramming (LIRE) system is developed based on a photoreceptor protein cryptochrome system and clustered regularly interspaced short palindromic repeats/nuclease‐deficient CRISPR‐associated protein 9 for induced PSCs reprogramming. This system enables remote, non‐invasive optogenetical regulation of endogenous Sox2 and Oct4 loci to reprogram mouse embryonic fibroblasts into iPSCs (iPSCLIRE) under light‐emitting diode‐based illumination. iPSCLIRE cells can be efficiently differentiated into different cells by upregulating a corresponding TF. iPSCLIRE cells are used for blastocyst injection and optogenetic chimeric mice are successfully generated, which enables non‐invasive control of user‐defined endogenous genes in vivo, providing a valuable tool for facile and traceless controlled gene expression studies and genetic screens in mice. This LIRE system offers a remote, traceless, and non‐invasive approach for cellular reprogramming and modeling of complex human diseases in basic biological research and regenerative medicine applications. |
| first_indexed | 2024-03-12T01:27:25Z |
| format | Article |
| id | doaj.art-9546ebbefec046f1b6d995d193e62074 |
| institution | Directory Open Access Journal |
| issn | 2198-3844 |
| language | English |
| last_indexed | 2024-03-12T01:27:25Z |
| publishDate | 2023-02-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj.art-9546ebbefec046f1b6d995d193e620742023-09-12T14:40:47ZengWileyAdvanced Science2198-38442023-02-01104n/an/a10.1002/advs.202202858An Optogenetic‐Controlled Cell Reprogramming System for Driving Cell Fate and Light‐Responsive Chimeric MiceMeiyan Wang0Yuanxiao Liu1Ziwei Wang2Longliang Qiao3Xiaoding Ma4Lingfeng Hu5Deqiang Kong6Yuan Wang7Haifeng Ye8Shanghai Frontiers Science Center of Genome Editing and Cell Therapy Biomedical Synthetic Biology Research Center Shanghai Key Laboratory of Regulatory Biology Institute of Biomedical Sciences and School of Life Sciences East China Normal University Dongchuan Road 500 Shanghai 200241 ChinaShanghai Frontiers Science Center of Genome Editing and Cell Therapy Biomedical Synthetic Biology Research Center Shanghai Key Laboratory of Regulatory Biology Institute of Biomedical Sciences and School of Life Sciences East China Normal University Dongchuan Road 500 Shanghai 200241 ChinaShanghai Frontiers Science Center of Genome Editing and Cell Therapy Biomedical Synthetic Biology Research Center Shanghai Key Laboratory of Regulatory Biology Institute of Biomedical Sciences and School of Life Sciences East China Normal University Dongchuan Road 500 Shanghai 200241 ChinaShanghai Frontiers Science Center of Genome Editing and Cell Therapy Biomedical Synthetic Biology Research Center Shanghai Key Laboratory of Regulatory Biology Institute of Biomedical Sciences and School of Life Sciences East China Normal University Dongchuan Road 500 Shanghai 200241 ChinaShanghai Frontiers Science Center of Genome Editing and Cell Therapy Biomedical Synthetic Biology Research Center Shanghai Key Laboratory of Regulatory Biology Institute of Biomedical Sciences and School of Life Sciences East China Normal University Dongchuan Road 500 Shanghai 200241 ChinaShanghai Frontiers Science Center of Genome Editing and Cell Therapy Biomedical Synthetic Biology Research Center Shanghai Key Laboratory of Regulatory Biology Institute of Biomedical Sciences and School of Life Sciences East China Normal University Dongchuan Road 500 Shanghai 200241 ChinaShanghai Frontiers Science Center of Genome Editing and Cell Therapy Biomedical Synthetic Biology Research Center Shanghai Key Laboratory of Regulatory Biology Institute of Biomedical Sciences and School of Life Sciences East China Normal University Dongchuan Road 500 Shanghai 200241 ChinaDepartment of Animal Sciences, College of Agriculture and Natural Resources Michigan State University East Lansing MI 48824 USAShanghai Frontiers Science Center of Genome Editing and Cell Therapy Biomedical Synthetic Biology Research Center Shanghai Key Laboratory of Regulatory Biology Institute of Biomedical Sciences and School of Life Sciences East China Normal University Dongchuan Road 500 Shanghai 200241 ChinaAbstract Pluripotent stem cells (PSCs) hold great promise for cell‐based therapies, disease modeling, and drug discovery. Classic somatic cell reprogramming to generate induced pluripotent stem cells (iPSCs) is often achieved based on overexpression of transcription factors (TFs). However, this process is limited by side effect of overexpressed TFs and unpredicted targeting of TFs. Pinpoint control over endogenous TFs expression can provide the ability to reprogram cell fate and tissue function. Here, a light‐inducible cell reprogramming (LIRE) system is developed based on a photoreceptor protein cryptochrome system and clustered regularly interspaced short palindromic repeats/nuclease‐deficient CRISPR‐associated protein 9 for induced PSCs reprogramming. This system enables remote, non‐invasive optogenetical regulation of endogenous Sox2 and Oct4 loci to reprogram mouse embryonic fibroblasts into iPSCs (iPSCLIRE) under light‐emitting diode‐based illumination. iPSCLIRE cells can be efficiently differentiated into different cells by upregulating a corresponding TF. iPSCLIRE cells are used for blastocyst injection and optogenetic chimeric mice are successfully generated, which enables non‐invasive control of user‐defined endogenous genes in vivo, providing a valuable tool for facile and traceless controlled gene expression studies and genetic screens in mice. This LIRE system offers a remote, traceless, and non‐invasive approach for cellular reprogramming and modeling of complex human diseases in basic biological research and regenerative medicine applications.https://doi.org/10.1002/advs.202202858cell reprogrammingchimeric miceendogenous transcription factorsoptogeneticsregenerative medicines |
| spellingShingle | Meiyan Wang Yuanxiao Liu Ziwei Wang Longliang Qiao Xiaoding Ma Lingfeng Hu Deqiang Kong Yuan Wang Haifeng Ye An Optogenetic‐Controlled Cell Reprogramming System for Driving Cell Fate and Light‐Responsive Chimeric Mice Advanced Science cell reprogramming chimeric mice endogenous transcription factors optogenetics regenerative medicines |
| title | An Optogenetic‐Controlled Cell Reprogramming System for Driving Cell Fate and Light‐Responsive Chimeric Mice |
| title_full | An Optogenetic‐Controlled Cell Reprogramming System for Driving Cell Fate and Light‐Responsive Chimeric Mice |
| title_fullStr | An Optogenetic‐Controlled Cell Reprogramming System for Driving Cell Fate and Light‐Responsive Chimeric Mice |
| title_full_unstemmed | An Optogenetic‐Controlled Cell Reprogramming System for Driving Cell Fate and Light‐Responsive Chimeric Mice |
| title_short | An Optogenetic‐Controlled Cell Reprogramming System for Driving Cell Fate and Light‐Responsive Chimeric Mice |
| title_sort | optogenetic controlled cell reprogramming system for driving cell fate and light responsive chimeric mice |
| topic | cell reprogramming chimeric mice endogenous transcription factors optogenetics regenerative medicines |
| url | https://doi.org/10.1002/advs.202202858 |
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