An engineered Sox17 induces somatic to neural stem cell fate transitions independently from pluripotency reprogramming
Advanced strategies to interconvert cell types provide promising avenues to model cellular pathologies and to develop therapies for neurological disorders. Yet, methods to directly transdifferentiate somatic cells into multipotent induced neural stem cells (iNSCs) are slow and inefficient, and it is unclear whether cells pass through a pluripotent state with full epigenetic reset. We report iNSC reprogramming from embryonic and aged mouse fibroblasts as well as from human blood using an engineered Sox17 (eSox17FNV). eSox17FNV efficiently drives iNSC reprogramming while Sox2 or Sox17 fail. eSox17FNV acquires the capacity to bind different protein partners on regulatory DNA to scan the genome more efficiently and has a more potent transactivation domain than Sox2. Lineage tracing and time-resolved transcriptomics show that emerging iNSCs do not transit through a pluripotent state. Our work distinguishes lineage from pluripotency reprogramming with the potential to generate more authentic cell models for aging-associated neurodegenerative diseases.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:9 |
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| Enthalten in: |
Science advances - 9(2023), 34 vom: 25. Aug., Seite eadh2501 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Weng, Mingxi [VerfasserIn] |
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| Links: |
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| Themen: |
HMGB Proteins |
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| Anmerkungen: |
Date Completed 25.08.2023 Date Revised 21.09.2023 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1126/sciadv.adh2501 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM361095406 |
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| 245 | 1 | 3 | |a An engineered Sox17 induces somatic to neural stem cell fate transitions independently from pluripotency reprogramming |
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| 500 | |a Date Revised 21.09.2023 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Advanced strategies to interconvert cell types provide promising avenues to model cellular pathologies and to develop therapies for neurological disorders. Yet, methods to directly transdifferentiate somatic cells into multipotent induced neural stem cells (iNSCs) are slow and inefficient, and it is unclear whether cells pass through a pluripotent state with full epigenetic reset. We report iNSC reprogramming from embryonic and aged mouse fibroblasts as well as from human blood using an engineered Sox17 (eSox17FNV). eSox17FNV efficiently drives iNSC reprogramming while Sox2 or Sox17 fail. eSox17FNV acquires the capacity to bind different protein partners on regulatory DNA to scan the genome more efficiently and has a more potent transactivation domain than Sox2. Lineage tracing and time-resolved transcriptomics show that emerging iNSCs do not transit through a pluripotent state. Our work distinguishes lineage from pluripotency reprogramming with the potential to generate more authentic cell models for aging-associated neurodegenerative diseases | ||
| 650 | 4 | |a Journal Article | |
| 650 | 7 | |a Sox17 protein, mouse |2 NLM | |
| 650 | 7 | |a HMGB Proteins |2 NLM | |
| 650 | 7 | |a SOXF Transcription Factors |2 NLM | |
| 700 | 1 | |a Hu, Haoqing |e verfasserin |4 aut | |
| 700 | 1 | |a Graus, Matthew S |e verfasserin |4 aut | |
| 700 | 1 | |a Tan, Daisylyn Senna |e verfasserin |4 aut | |
| 700 | 1 | |a Gao, Ya |e verfasserin |4 aut | |
| 700 | 1 | |a Ren, Shimiao |e verfasserin |4 aut | |
| 700 | 1 | |a Ho, Derek Hoi Hang |e verfasserin |4 aut | |
| 700 | 1 | |a Langer, Jakob |e verfasserin |4 aut | |
| 700 | 1 | |a Holzner, Markus |e verfasserin |4 aut | |
| 700 | 1 | |a Huang, Yuhua |e verfasserin |4 aut | |
| 700 | 1 | |a Ling, Guang Sheng |e verfasserin |4 aut | |
| 700 | 1 | |a Lai, Cora Sau Wan |e verfasserin |4 aut | |
| 700 | 1 | |a Francois, Mathias |e verfasserin |4 aut | |
| 700 | 1 | |a Jauch, Ralf |e verfasserin |4 aut | |
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