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Direct conversion of adult skin fibroblasts to endothelial cells by defined factors

ABSTRACT: We directly converted mouse adult skin fibroblasts (SFBs) into induced endothelial cells (iECs) by transduction of 5 key factors. We analyzed the genome-wide gene expression profile of iECs, and compared it with those of negative controls (original SFBs, mock-infected SFBs) or those of positive controls (primary endothelial cells from lungs of mice, MS-1 endothelial cell line).

ORGANISM(S): Mus musculus

PROVIDER: GSE50071 | GEO | 2019/08/09

REPOSITORIES: GEO

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Generation of neural crest cells by direct lineage conversion

Project description:Neural crest cells (NC cells) are multipotent cells that emerge from the dorsal region of a fusing neural tube and migrate throughout the developing embryo. Due to their multipotency and divergent roles during embryogenesis, the generation and differentiation of NC cells should be elucidated in more detail. However, difficulties have been associated with isolating and manipulating NC cells for investigation because a limited number of NC cells are generated in a short period of embryogenesis. To overcome this issue, we attempted to directly convert mouse fibroblasts into NC cells using transcription factors specifically expressed in NC cells. We analyzed the molecular profiles of NC cells and neural tube cells in 9.5-day mouse embryos, and identified the transcription factors that were strongly expressed in NC cells. Among these transcription factors, Sox10 together with c-Myc and Klf4 directly converted mouse fibroblasts into NC cells. The converted NC cells differentiated into neurons, glial cells, smooth muscle cells, adipocytes, and osteoblasts, exhibiting differentiation abilities similar to those of in vivo NC cells. They also displayed a self-renewal ability while maintaining their differentiation ability. In in ovo transplantation, the converted NC cells migrated along NC cell migration pathways. Therefore, directly converted NC cells can contribute to the progression of NC cell studies.

2017-02-10 | GSE63896 | GEO

Direct conversion of fibroblasts to functional neurons by defined factors.

Project description: Not available

| S-EPMC2829121 | biostudies-literature

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

Direct conversion of human fibroblasts into functional osteoblasts by defined factors.

Project description: Not available

| S-EPMC4434770 | biostudies-literature

Conversion of mouse fibroblast to hepatocyte-like cells by defined factors

Project description:Plasticity of differentiated cells has been proved by nuclear transfer, induced pluripotent cells and transdifferentiation. Here we show that by transduction of 3 factors (Hnf1alpha, Gata4, and Foxa3) and p19Arf inactivation, tail-tip fibroblasts can be converted to hepatocyte-like (iHep) cells, expressing hepatocyte marker genes, and acquiring many mature hepatocyte functions in vitro and in vivo.

2011-05-11 | GSE23635 | GEO

Rapid conversion of fibroblasts into functional forebrain GABAergic interneurons by direct genetic reprogramming

Project description:Transplantation of GABAergic interneurons (INs) can sustain long-standing benefits in animal models of epilepsy and other neurological disorders. In a therapeutic perspective, a renewable source of functional GABAergic INs is needed. Here, we identified five factors (Foxg1, Sox2, Ascl1, Dlx5 and Lhx6) able to convert fibroblasts directly into induced GABAergic INs (iGABA-INs), displaying the molecular signature of telencephalic INs. The selected factors recapitulate in fibroblasts the activation of transcriptional networks required for the specification of GABAergic fate during telencephalon development. iGABA-INs exhibited progressively maturing firing patterns comparable to those of cortical INs, had synaptic currents and released GABA. Importantly, upon grafting in the hippocampus, iGABA-INs survived, matured and their optogenetic stimulation triggered GABAergic transmission and inhibited the activity of connected granule cells. The five factors also converted human cells into functional GABAergic neurons. These properties define iGABA-INs as a promising tool for disease modeling and cell-based therapeutic approaches. Comparison of iGABA-INs transcriptional profile with those of starting fibroblasts and GAD67-GFP+ cortical interneurons.

2015-12-15 | E-GEOD-74065 | biostudies-arrayexpress

Direct conversion of fibroblasts into functional astrocytes by defined transcription factors.

Project description: Not available

| S-EPMC4297873 | biostudies-other

Conversion of human fibroblast to endothelial cell by defined factors

2012-12-03 | GSE42672 | GEO

DIRECT CONVERSION OF FIBROBLASTS INTO FUNCTIONAL ASTROCYTES BY DEFINED TRANSCRIPTION FACTORS

Project description:Direct cell reprogramming has enabled the direct conversion of skin fibroblasts into functional neurons and oligodendrocytes using a minimal set of cell lineage-specific transcription factors. This approach has substantial advantages since it is rapid and simple, generating the cell type of interest in a single step. However, it remains unknown whether this technology can be applied for directly reprogramming skin cells into astrocytes, the third neural lineage. Astrocytes play crucial roles in neuronal homeostasis and their dysfunctions contribute to the origin and progression of multiple human diseases. Herein, we carried out a screening using several transcription factors involved in defining the astroglial cell fate and identified NFIA, NFIB and SOX9 to be sufficient to convert with high efficiency embryonic and post-natal mouse fibroblasts into astrocytes (iAstrocytes). We proved both by gene expression profiling and functional tests that iAstrocytes are comparable to native brain astrocytes. This protocol can be then employed to generate functional iAstrocytes for a wide range of experimental applications. Induced astrocytes (iAstro) were compared to Fibroblasts (Fibro) as negative control and to primary astrocytes (astro) as positive control. Three biological replicates were analyzed for each experimental group.

2015-06-22 | E-GEOD-59018 | biostudies-arrayexpress

Rapid conversion of fibroblasts into functional forebrain GABAergic interneurons by direct genetic reprogramming

2015-12-15 | GSE74065 | GEO

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