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An engineered Sox17 induces somatic to neural stem cell fate transition independently from pluripotency reprogramming

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus Homo sapiens

PROVIDER: GSE195556 | GEO | 2023/07/19

REPOSITORIES: GEO

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An engineered Sox17 induces somatic to neural stem cell fate transitions independently from pluripotency reprogramming.

Project description: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.

| S-EPMC10446497 | biostudies-literature

An engineered Sox17 induces somatic to neural stem cell fate transition independently from pluripotency reprogramming [RRBS]

Project description:Advances in molecular strategies to reprogram cell fate is a promising avenue for cell-based therapies. Methods to generate induced neural stem cells (iNSCs) are often slow with limited reprogramming events and it is unclear whether cells transit via a pluripotent state. We report an iNSC reprogramming approach from embryonic and aged mouse fibroblasts using an engineered Sox17 (eSox17FNV). eSox17FNV efficiently drives iNSC reprogramming while Sox2 or Sox17 fails to do so. eSox17FNV acquires the capacity to bind new protein partners to scan the genome more efficiently and possesses a more potent transactivation domain than Sox2. At the onset of reprogramming, in the presence of eSox17FNV, fibroblasts divert from a iPSC route towards iNSC fate. Further, lineage tracing shows that emerging iNSCs do not transit through a pluripotent state if POU factors are excluded. This reveals new molecular and physiological framework for iNSC generation and contrasts with lineage from pluripotency reprogramming.

2023-07-19 | GSE225305 | GEO

An engineered Sox17 induces somatic to neural stem cell fate transition independently from pluripotency reprogramming [scRNA-seq]

2023-07-19 | GSE225306 | GEO

An engineered Sox17 induces somatic to neural stem cell fate transition independently from pluripotency reprogramming [ATAC-Seq]

2023-07-19 | GSE195554 | GEO

An engineered Sox17 induces somatic to neural stem cell fate transition independently from pluripotency reprogramming [RNA-seq]

2023-07-19 | GSE195551 | GEO

An engineered Sox17 induces somatic to neural stem cell fate transition independently from pluripotency reprogramming [RNA-seq III]

2023-07-19 | GSE225830 | GEO

An engineered Sox17 induces somatic to neural stem cell fate transition independently from pluripotency reprogramming [RNA-seq II]

2023-07-19 | GSE225829 | GEO

An engineered Sox17 induces somatic to neural stem cell fate transition independently from pluripotency reprogramming

Project description:An engineered Sox17 induces somatic to neural stem cell fate transition independently from pluripotency reprogramming

| PRJNA801239 | ENA

An engineered Sox17 induces somatic to neural stem cell fate transition independently from pluripotency reprogramming [RRBS]

Project description:An engineered Sox17 induces somatic to neural stem cell fate transition independently from pluripotency reprogramming [RRBS]

| PRJNA934927 | ENA

An engineered Sox17 induces somatic to neural stem cell fate transition independently from pluripotency reprogramming [scRNA-seq]

Project description:An engineered Sox17 induces somatic to neural stem cell fate transition independently from pluripotency reprogramming [scRNA-seq]

| PRJNA934928 | ENA

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