Ontology highlight
ABSTRACT:
PROVIDER: PRJNA476303 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR7347190_1.fastq.gz | Fastqsanger.gz | |||
| SRR7347190_2.fastq.gz | Fastqsanger.gz | |||
| SRR7347191_1.fastq.gz | Fastqsanger.gz | |||
| SRR7347191_2.fastq.gz | Fastqsanger.gz | |||
| SRR7347192_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 18 |
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Project description:Small molecules enable highly efficient neuronal conversion of human fibroblasts
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Project description:Conversion of fibroblasts to functional Leydig like cells using defined small molecules
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Project description:Recent studies have shown that defined hepatic factors could lead to the direct conversion of fibroblasts into induced hepatocytes (iHeps). However, reported conversion efficiencies are vey low and the underlying mechanism of the hepatic lineage conversion is largely unknown. Here, we report that direct conversion into iHeps is a stepwise transition involving erasure of somatic memory, mesenchymal-to-epithelial transition, and induction of hepatic cell fate in a sequential manner. Throughout screening for additional factors that could potentially enhance the kinetics of the MET and hepatic programs, we have found that c-Myc and Klf4 (CK) dramatically accelerate the conversion kinetics, resulting in remarkably improved generation of iHeps (>87 fold). Furthermore, we identified small molecules that could replace the roles of CK and thus led to the highly efficient generation of iHeps without CK. Finally, we show that a single factor (Hnf1α) supported by small molecules is sufficient to robustly induce transprogramming of fibroblasts into functional hepatocyte-like cells with high yield. This novel approach might help to fully elucidate the direct conversion process and also facilitate the translation of iHep into clinic.
2013-12-03 | GSE52566 | GEO
Project description:Forced expression of pro-neural transcription factors was shown to mediate direct neuronal conversion of human fibroblasts. Since neurons are postmitotic, the conversion efficiency represents an important parameter. Here we present a minimalist approach combining two factor neuronal programming with small molecule-based inhibition of GSK3ß and SMAD signaling, which gives rise to functional neuron-like cells (iNs) of various neurotransmitter phenotypes with an overall yield of up to >200% and a final neuronal purity of up to >80%. Timcourse of reprogramming of fibroblasts towards an neuronal phenotype in two independent fibroblast lines
2012-04-07 | E-GEOD-36246 | biostudies-arrayexpress
Project description:Direct conversion of somatic cells into neurons holds great promise for regenerative medicine. However, neuronal conversion is relatively inefficient in human cells compared to mouse cells. It has been unclear what might be the key barriers to reprogramming in human cells. We recently elucidated an RNA program mediated by the polypyrimidine tract binding protein PTB to convert mouse embryonic fibroblasts (MEFs) into functional neurons. In human adult fibroblasts (HAFs), however, we unexpectedly found that invoking the documented PTB–REST–miR-124 loop generates only immature neurons. We now report that the functionality requires sequential inactivation of PTB and the PTB paralog nPTB in HAFs. Inactivation of nPTB triggers another self-enforcing loop essential for neuronal maturation, which comprises nPTB, the transcription factor BRN2, and miR-9. These findings suggest that two separate gatekeepers control neuronal conversion and maturation and consecutively overcoming these gatekeepers enables deterministic reprogramming of HAFs into functional neurons.
2016-04-25 | GSE74814 | GEO
Project description:Here we performed the first combinatorial small molecule screen for the rapid conversion of hPSCs into postmitotic neurons. We identified a combination of five small molecule pathway inhibitors sufficient to yield neurons at > 75% efficiency within 10 days of differentiation in the absence of any recombinant growth factors. The resulting human neurons express canonical markers of nociceptive sensory fate. Two treatments (LSB and 3i) at days 2,3,5,7,9, and 15, in triplicate
2011-04-01 | E-GEOD-26867 | biostudies-arrayexpress
Project description:Direct reprogramming approaches offer an attractive alternative to stem-cell-derived models, allowing the retention of epigenetic information and age-associated cellular phenotypes. To explore such age-related phenotypes, several groups have generated multiple neuronal subtypes, neural progenitor cells, oligodendrocytes, and other cell types directly from fibroblasts. Other groups have had success at the efficient conversion of embryonic fibroblasts to astrocytes but have not yet achieved similar conversion efficiency for adult human fibroblasts. In order to generate astrocytes for the study of age-related diseases, we developed an improved direct conversion strategy employing a combination of small molecules to activate specific pathways that induce trans-differentiation of human adult fibroblasts to astrocytes. We demonstrate that this method produces mature GFAP+/S100β+ cells at high efficiency (40-45%), comparable to previous studies utilizing embryonic fibroblasts. Further, Fibroblast-derived induced Astrocytes (FdiAs) are enriched for markers of astrocyte functionality, including ion-channel buffering, gap-junction communication, and glutamate uptake; and exhibit astrocyte-like calcium signaling and neuroinflammatory phenotypes. RNA-Seq analysis indicates an adult rather than fetal astrocytic gene expression signature, with a greater correlation to temporal lobe astrocytes. Fibroblast-derived induced astrocytes provide a useful tool in understanding age-associated disease processes and complement existing in vitro models of induced neurons (iNs), providing an additional platform to study late-stage brain disorders.
2024-08-31 | GSE239320 | GEO
Project description:Direct reprogramming approaches offer an attractive alternative to stem-cell-derived models, allowing the retention of epigenetic information and age-associated cellular phenotypes, as well as a fast method to reach a target cell type. Several groups have previously generated multiple neuronal subtypes, neural progenitor cells, oligodendrocytes, and other cell types directly from fibroblasts. Other groups have had success at the efficient conversion of embryonic fibroblasts to astrocytes but have not yet achieved similar conversion efficiency for adult human fibroblasts. In order to generate astrocytes for the study of adult-stage disorders, we developed an improved direct conversion strategy employing a combination of small molecules to activate specific pathways that induce trans-differentiation of human adult fibroblasts to astrocytes. We demonstrate that this method produces mature GFAP+/S100β+ cells at high efficiency (40-45%), comparable to previous studies utilizing embryonic fibroblasts. Further, Fibroblast-derived induced Astrocytes (FdiAs) are enriched for markers of astrocyte functionality, including ion-channel buffering, gap-junction communication, and glutamate uptake; and exhibit astrocyte-like calcium signaling and neuroinflammatory phenotypes. RNA-Seq analysis indicates an adult rather than fetal astrocytic gene expression signature, with a greater correlation to temporal lobe astrocytes. Fibroblast-derived induced astrocytes provide a useful tool in studying the adult brain and complement existing in vitro models of induced neurons (iNs), providing an additional platform to study late-stage brain disorders.
2024-07-19 | GSE272279 | GEO