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.
Direct conversion of fibroblasts into functional astrocytes by defined transcription factors.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
TFEB controls cellular lipid metabolism through a starvation-induced autoregulatory loop.
Specimen part
View SamplesThe role of the transcription factor EB (TFEB) in the control of cellular functions, including in vascular bed, is mostly thought to be the regulation of lysosomal biogenesis and autophagic flux. While this is its best-known function, we report here the ability of TFEB to orchestrate a non-canonical program involved in the control of cell-cycle and VEGFR2 pathway in the developing vasculature. In endothelial cells, TFEB deletion halts proliferation by inhibiting the CDK4/Rb pathway, which regulates the cell cycle G1-S transition. In an attempt to overcome this limit, cells compensate by increasing the amount of VEGFR2 on the plasma membrane through a microRNA-mediated mechanism and the control of its membrane trafficking. TFEB transactivates the miR-15a/16-1 cluster, which limits the stability of the VEGFR2 transcript, and negatively modulates the expression of MYO1C, which regulates VEGFR2 delivery to the cell surface. In TFEB knocked-down cells, the reduced and increased amount respectively of miR-15a/16-1 and MYO1C result in the overexpression on plasmamembrane of VEGFR2, which however shows low signaling strength. Using endothelial loss-of-function Tfeb mouse mutants, we present evidence of defects in fetal and newborn mouse vasculature caused by the reduced endothelial proliferation and by the anomalous function of VEGFR2 pathway. Thus, this study revealed a new and unreported function of TFEB that expands its role beyond the regulation of autophagic pathway in the vascular system.
TFEB controls vascular development by regulating the proliferation of endothelial cells.
Cell line
View SamplesExpression data from Ppara (peroxisome proliferator activated receptor alpha) KO mice injected with TFEB specifically in liver. In order to identify the effects of TFEB overexpression together with Ppara absence on the liver transcriptome, we performed Affymetrix Gene-Chip hybridization experiments for the injected mice
TFEB controls cellular lipid metabolism through a starvation-induced autoregulatory loop.
Specimen part
View SamplesIn order to identify the effects of TFEB overexpression on the liver transcriptome, we performed Affymetrix Gene-Chip hybridization experiments for the injected mice
TFEB controls cellular lipid metabolism through a starvation-induced autoregulatory loop.
Specimen part
View SamplesIn order to identify the effects of starvation on the liver transcriptome, we performed Affymetrix Gene-Chip hybridization experiments for the starved mice
TFEB controls cellular lipid metabolism through a starvation-induced autoregulatory loop.
Specimen part, Treatment
View SamplesIn order to identify the effects of transcription factor EB (TFEB) overexpression on the liver transcriptome, we performed Affymetrix GeneChip hybridization experiments on injected mice overexpressing TFEB specifically in the liver.
TFEB controls cellular lipid metabolism through a starvation-induced autoregulatory loop.
Age, Specimen part, Treatment
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Lysosomal calcium signalling regulates autophagy through calcineurin and TFEB.
Cell line
View SamplesIn order to identify the effects of starvation on the PPP3R1 cell line trascriptome, we performed Affymetrix Gene-Chip hybridization experiments for the starved cells
Lysosomal calcium signalling regulates autophagy through calcineurin and TFEB.
Cell line
View SamplesIn order to identify the effects of Tcfeb overexpression on the kidney transcriptome, we performed Affymetrix Gene-Chip hybridization experiments for the double heterozygous KSP_CRE/KSP_Tcfeb 14 days old mice as compared to control KSP_CRE mice
Modelling TFE renal cell carcinoma in mice reveals a critical role of WNT signaling.
Specimen part
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