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Generation of functional human oligodendrocytes from dermal fibroblasts by direct lineage conversion

ABSTRACT: Generation of functional human oligodendrocytes from dermal fibroblasts by direct lineage conversion

PROVIDER: PRJNA840883 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR19332572_1.fastq.gz	Fastqsanger.gz
	SRR19332572_2.fastq.gz	Fastqsanger.gz
	SRR19332573_1.fastq.gz	Fastqsanger.gz
	SRR19332573_2.fastq.gz	Fastqsanger.gz
	SRR19332574_1.fastq.gz	Fastqsanger.gz

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Generation of functional human oligodendrocytes from dermal fibroblasts by direct lineage conversion

Project description:We report the generation of myelinating human oligodendrocytes from dermal fibroblasts using a direct lineage conversion technique.

2022-05-20 | GSE203451 | GEO

Direct conversion of fibroblasts to neurons by a new mechanism – p53 regulation

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Direct conversion of fibroblasts to neurons by a new mechanism – p53 regulation

Project description:Direct conversion from fibroblast to neuron has recently been successfully induced bypassing the pluripotent state. However, the conversion takes a few months with low percentages of success. Here we found that depletion of p53, which can converted fibroblasts into three major neural lineages: neurons, astrocytes and oligodendrocytes. Furthermore, our method provided a high efficiency of conversion in aging fibroblasts, where published methods failed. This finding may help developing a prototype for neuron replacement therapy, including foraging people vulnerable to neurological disorders. p53 has been shown to inhibit reprogramming of fibroblasts to iPS cells, by depletion of p53 in human fibroblasts, we study the function of p53 in induced neuron process. By induction of p53 knockdown fibroblasts with special neuron medium, we can get mature neurons directly. In the induction process, many neurogenic transcription factors were up-regulated, and we prove that p21 is not involved in this process.

2013-04-26 | E-GEOD-46392 | biostudies-arrayexpress

Spontaneous direct fate conversion of neuroblasts into oligodendrocytes upon demyelination in the adult mouse brain

Project description:After demyelinating insult, the neuronal progenitors of the adult mouse sub-ventricular zone (SVZ) called neuroblasts convert into oligodendrocytes that participate to the remyelination process. We use this rare example of spontaneous fate conversion to identify the molecular mechanisms governing these processes. Using single cell RNA-sequencing, we show that SVZ neuroblasts fate conversion proceeds directly, through formation of a non-proliferating transient cellular state co-expressing markers of both neuronal and oligodendrocyte identities. Transition between the two identities starts immediately after demyelination and occurs gradually, by a stepwise upregulation/downregulation of key TFs and chromatin modifiers. Each step of this fate conversion involves fine adjustments of the transcription and translation machineries as well as tight regulation of metabolism and migratory behaviors. Together, these data constitute the first in-depth analysis of a spontaneous direct cell fate conversion in the adult mammalian CNS.

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Direct Cell Conversion of Human Fibroblasts to Monocytic phagocytes by Forced Expression of Monocytic Regulatory Network Elements

Project description:Direct cell conversion is now expected to apply to therapeutic purposes. Although that has been succeeded in several cell types, the mechanism or general way to identify the key transcription factors are still unclear. In addition, most of the cases are not completely identical with the target cells. In previous work, we suggested that cell status is maintained by a homeostatic network of limited number of TFs and no single transcription factor is both necessary and sufficient to drive the differentiation process. Here, identifying the key TFs of human monocyte by combining comparative gene expression analysis and literature based text-mining, we mimicked the monocytic regulatory network in human dermal fibroblasts to induce direct cell conversion of the fibroblasts to monocytes. We suggested that although it is a primary master TF, single TF is not sufficient to induce the direct cell conversion and orchestrated TF regulation is necessary to complete the cell conversion. Total RNA obtained from human dermal fibroblasts(FIB), human CD14+ monocytes(MON), mock lentivirus vector transduced fibroblasts (FIB-mock), SPI1 transduced fibroblasts (FIB-SPI1), and SPI1, CEBPA, MNDA, IRF8 transduced fibroblasts(FIB-4Fs). The fold change was computed compared with fibroblasts or FIB-mock.

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Direct cell conversion from human dermal fibroblast to adipocyte

Project description:To investigate the effect of ZNF395 on adipogenesis, we tested whether ZNF395 enhance cell conversion from human dermal Fibroblast (FIB) to Adipocyte (ADP). PPARG2 was reported as a master regulator and can induce adipogenesis in non-adipogenic fibroblasts. We transduced PPARG2 with or without ZNF395 in FIB with lentivirus. Interestingly, co-transduction of PPARG2 and ZNF395 showed higher occurrence of adipocyte-like cells as compared with PPARG2 alone. Moreover, genes related with lipid metabolic process and lipid transport was significantly up-regulated in combination of PPARG2 and ZNF395. These results suggest that ZNF395 co-ordinate the transcriptional regulatory pathway with PPARG2, necessary for the induction of adipogenesis. Total RNA was obteined from human dermal fibroblast transduced with mock lentivirus vector (FIB_ctrl), PPARG2 (FIB_PPARG2) and co-transduced with PPARG2 and ZNF395 (FIB_PPARG2+ZNF395).

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

ATAC-seq of in vitro reprogrammed mouse pericytes to oligodendrocytes

Project description:Direct conversion of pericytes (PCs) into induced oligodendrocytes (iOPCs) by ectopic expression of Olig2 and Sox10 (2F) was assessed by chromatin accessibility profiling (by ATAC-seq). Samples were collected before and after direct conversion (at 3 different time points/passages - p5, p15 and p25).

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Direct Cell Conversion of Human Fibroblasts to Monocytic phagocytes by Forced Expression of Monocytic Regulatory Network Elements

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