Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Lineage conversion induced by pluripotency factors involves transient passage through an iPSC stage

ABSTRACT: Brief expression of pluripotency-associated factors such as Oct4, Klf4, Sox2 and c-Myc (OKSM), in combination with differentiation-inducing signals, has been reported to trigger transdifferentiation of fibroblasts into other cell types. Here we show that OKSM expression in mouse fibroblasts gives rise to both induced pluripotent stem cells (iPSCs) and induced neural stem cells (iNSCs) under conditions previously shown to induce only iNSCs. Fibroblast-derived iNSC colonies silenced retroviral transgenes and reactivated silenced X chromosomes, both hallmarks of pluripotent stem cells. Moreover, lineage tracing with an Oct4-CreER labeling system demonstrated that virtually all iNSC colonies originated from cells transiently expressing Oct4, whereas ablation of Oct4+ cells prevented iNSC formation. Lastly, an alternative transdifferentiation cocktail that lacks Oct4 and was reportedly unable to support induced pluripotency yielded iPSCs and iNSCs carrying the Oct4-CreER-derived lineage label. Together, these data suggest that iNSC generation from fibroblasts using OKSM and other pluripotency-related reprogramming factors requires passage through a transient iPSC state.

ORGANISM(S): Mus musculus

PROVIDER: GSE65951 | GEO | 2015/04/30

SECONDARY ACCESSION(S): PRJNA275545

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Pluripotency factor-induced lineage conversion involves transient passage through an iPS cell stage

Project description:Brief expression of pluripotency-associated factors such as OCT4, KLF4, SOX2 and c-MYC (OKSM), in combination with differentiation-inducing signals, was reported to trigger transdifferentiation of fibroblasts into alternative cell types. Here, we show that OKSM expression gives rise to both induced pluripotent stem cells (iPSCs) and iNSCs under conditions that were previously shown to induce only NSC transdifferentiation. Fibroblast-derived iNSC colonies silenced retroviral transgenes and reactivated silenced X chromosomes, both hallmarks of pluripotent stem cells. Moreover, lineage tracing via an Oct4-CreER labeling system demonstrated that virtually all iNSC colonies originate from cells transiently expressing Oct4, whereas ablation of Oct4-positive cells prevented iNSC formation. Lastly, use of an alternative transdifferentiation cocktail that lacks OCT4 and was reportedly unable to support induced pluripotency, yielded iPSCs and iNSCs carrying the Oct4-CreER-derived lineage label. Together, these data suggest that iNSC generation using OKSM and related reprogramming factors requires passage through a transient iPSC state. 5 samples were anlyzed in total, 2 induced pluripotent stem cells (iPSCs), 1 neural stem cells (NSCs) and 2 induced NSCs (iNSCs)

2015-04-30 | E-GEOD-65951 | biostudies-arrayexpress

Fusion of reprogramming factors alters trajectory of somatic lineage conversion

Project description:Simultaneous expression of Oct4, Klf4, Sox2, and cMyc induces pluripotency in somatic cells (iPSCs). Replacing Oct4 with the neuro-specific factor Brn4 leads to the transdifferentiation of fibroblasts into induced neural stem cells (iNSCs). However, Brn4 was recently found to induce a transient acquisition of pluripotency before establishing the neural fate. We employed genetic lineage tracing and found that induction of iNSCs with individual vectors leads to direct lineage conversion. In contrast, polycistronic expression produces a Brn4-Klf4 fusion protein that enables the induction of pluripotency. Our study demonstrates that a combination of pluripotency and tissue-specific factors allows for direct somatic cell transdifferentiation, bypassing the acquisition of a pluripotent state. This result has major implications for lineage conversion technologies, which hold potential for providing a safer alternative to iPSCs for clinical application both in vitro and in vivo.

2019-01-29 | GSE125740 | GEO

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

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 | 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 [scRNA-seq]

2023-07-19 | GSE225306 | GEO

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

2023-07-19 | GSE225305 | 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

Therapeutic potential of induced neural stem cells for spinal cord injury

Project description:The spinal cord does not spontaneously regenerate after injury and a treatment that ensures functional recovery after spinal cord injury (SCI) is still not available. Recently, fibroblasts have been directly converted into induced neural stem cells (iNSCs) following the forced expression of different combinations of transcription factors. Although directly converted iNSCs have been considered as a potentialcell source for clinical applications, their therapeutic potential has not been investigated yet. Here we show that iNSCs directly converted from mouse fibroblasts enhance the functional recovery after SCI in rats. Mouse embryonic fibroblasts (MEFs) were directly converted into iNSCs using four transcription factors (Brn4, Sox2, Klf4 and c-Myc). iNSCs showed gene expression profiles similar to cNSCs as determined by microarray analysis. MEFs were derived from C3H mouse strain embryos at embryonic day (E)13.5 after removing the head and all internal organs including the gonads and the spinal cord. 5x10^4 fibroblasts were transduced with replication-defective retroviral particles coding for Sox2, Klf4, c-Myc, and Brn4. After 48 h, the transduced fibroblasts were cultured in standard NSC medium. iNSC clusters were observed 4-5 weeks after transduction and expanded. Both MEFs and cNSCs were used as negative and positive control, respectively.

2013-10-01 | E-GEOD-51331 | biostudies-arrayexpress

Conversion of human fibroblast to endothelial cell by defined factors

Project description:Transient pluripotency-factor-based signaling-directed (TPS) transdifferentiation approach could be further applied to generate functional induced endothelial (iEnd) cells from human fibroblasts with only two factors: Oct4 and Klf4 (OK). The iEnd cells exhibit characteristic endothelial cell phenotype in vitro and in vivo and are capable of functionally promoting vascular regeneration and blood perfusion in a murine model of PAD. Human fibroblasts were transfected with Oct4 and Klf4 then changed to endothelial cell culture media with growth factors. iENDs were purified by FACS and enriched in EGM2 media.

2012-12-03 | E-GEOD-42672 | biostudies-arrayexpress

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data