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Characterisation of Multipotent Stem Cells Generated by Direct Conversion of Human Adipoctyes using PDGF-AB and 5-Azacytidine

ABSTRACT: Characterisation of Multipotent Stem Cells Generated by Direct Conversion of Human Adipoctyes using PDGF-AB and 5-Azacytidine

PROVIDER: PRJNA633382 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR11804641_1.fastq.gz	Fastqsanger.gz
	SRR11804641_2.fastq.gz	Fastqsanger.gz
	SRR11804642_1.fastq.gz	Fastqsanger.gz
	SRR11804642_2.fastq.gz	Fastqsanger.gz
	SRR11804643_1.fastq.gz	Fastqsanger.gz

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Induction of Muscle Regenerative Multipotent Stem Cells from Human Adipocytes by PDGF-AB and 5-Azacytidine

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Induction of Muscle Regenerative Multipotent Stem Cells from Human Adipocytes by PDGF-AB and 5-Azacytidine [RRBS]

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Induction of Muscle Regenerative Multipotent Stem Cells from Human Adipocytes by PDGF-AB and 5-Azacytidine [ChIP-seq]

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Induction of Muscle Regenerative Multipotent Stem Cells from Human Adipocytes by PDGF-AB and 5-Azacytidine [RRBS]

Project description:Terminally differentiated murine osteocytes and adipocytes can be reprogrammed using platelet-derived growth factor–AB and 5-Azacytidine into multipotent stem cells with stromal cell characteristics. To generate a product that is amenable for therapeutic application, we have modified and optimised culture conditions to reprogram human adipocytes into induced multipotent stem cells (iMS) and expand them in vitro. The basal transcriptomes of adipocyte-derived iMS cells and matched adipose-tissue-derived mesenchymal stem cells were remarkably similar. However, there were distinct changes in histone modifications and CpG methylation at cis-regulatory regions consistent with an epigenetic landscape that was primed for tissue development and differentiation. In a non-specific tissue injury xenograft model, iMS cells contributed directly to new muscle, bone, cartilage and blood vessels with no evidence of teratogenic potential. In a cardiotoxin muscle injury model, iMS cells contributed specifically to satellite cells and myofibres without ectopic tissue formation. Taken together, human adipocyte derived iMS cells regenerate tissues in a context dependent manner without ectopic or neoplastic growth.

2021-02-08 | GSE151526 | GEO

Induction of Muscle Regenerative Multipotent Stem Cells from Human Adipocytes by PDGF-AB and 5-Azacytidine [ChIP-seq]

2021-02-08 | GSE151525 | GEO

Characterisation of Multipotent Stem Cells Generated by Direct Conversion of Human Adipoctyes using PDGF-AB and 5-Azacytidine

Project description:This submission represents the RNAseq component of the study.

2021-02-08 | GSE150720 | GEO

PDGF-AB and 5-Azacytidine induce conversion of somatic cells into tissue-regenerative multipotent stem cells.

Project description:Current approaches in tissue engineering are geared toward generating tissue-specific stem cells. Given the complexity and heterogeneity of tissues, this approach has its limitations. An alternate approach is to induce terminally differentiated cells to dedifferentiate into multipotent proliferative cells with the capacity to regenerate all components of a damaged tissue, a phenomenon used by salamanders to regenerate limbs. 5-Azacytidine (AZA) is a nucleoside analog that is used to treat preleukemic and leukemic blood disorders. AZA is also known to induce cell plasticity. We hypothesized that AZA-induced cell plasticity occurs via a transient multipotent cell state and that concomitant exposure to a receptive growth factor might result in the expansion of a plastic and proliferative population of cells. To this end, we treated lineage-committed cells with AZA and screened a number of different growth factors with known activity in mesenchyme-derived tissues. Here, we report that transient treatment with AZA in combination with platelet-derived growth factor-AB converts primary somatic cells into tissue-regenerative multipotent stem (iMS) cells. iMS cells possess a distinct transcriptome, are immunosuppressive, and demonstrate long-term self-renewal, serial clonogenicity, and multigerm layer differentiation potential. Importantly, unlike mesenchymal stem cells, iMS cells contribute directly to in vivo tissue regeneration in a context-dependent manner and, unlike embryonic or pluripotent stem cells, do not form teratomas. Taken together, this vector-free method of generating iMS cells from primary terminally differentiated cells has significant scope for application in tissue regeneration.

| S-EPMC4843430 | biostudies-literature

Induction of muscle-regenerative multipotent stem cells from human adipocytes by PDGF-AB and 5-azacytidine.

Project description:Terminally differentiated murine osteocytes and adipocytes can be reprogrammed using platelet-derived growth factor-AB and 5-azacytidine into multipotent stem cells with stromal cell characteristics. We have now optimized culture conditions to reprogram human adipocytes into induced multipotent stem (iMS) cells and characterized their molecular and functional properties. Although the basal transcriptomes of adipocyte-derived iMS cells and adipose tissue-derived mesenchymal stem cells were similar, there were changes in histone modifications and CpG methylation at cis-regulatory regions consistent with an epigenetic landscape that was primed for tissue development and differentiation. In a non-specific tissue injury xenograft model, iMS cells contributed directly to muscle, bone, cartilage, and blood vessels, with no evidence of teratogenic potential. In a cardiotoxin muscle injury model, iMS cells contributed specifically to satellite cells and myofibers without ectopic tissue formation. Together, human adipocyte-derived iMS cells regenerate tissues in a context-dependent manner without ectopic or neoplastic growth.

| S-EPMC7806226 | biostudies-literature

Gene regulation in Erbb2 transfected NIH3T3 cells after Azacytidine treatment

Project description:5-Azacytidine or 5-aza-2’-deoxycytidine is a chemical analogue of the cytosine nucleoside used in DNA and RNA. Cells in the presence of 5-azacytidine incorporate it into DNA during replication and RNA during transcription. The incorporation of 5-azacytidine into DNA or RNA inhibits methyltransferase thereby causing demethylation in that sequence, affecting the way that cell regulation proteins are able to bind to the DNA/RNA substrate. Inhibition of DNA occurs through the formation of stable complexes between the molecule and with DNA methyltransferases, thereby saturating the cells methylation machinery. 5-azacytidine is mainly used in the treatment of myelodysplastic syndrome. Changes in gene expression levels in Erbb2 transfected murine fibroblast cell line after treatment with Azacytidine in two different concentrations were analysed. Keywords: cDNA microarray, murine fibroblast, azacytidine treatment, carcinogenesis

2009-10-01 | GSE8374 | GEO

PDGF and FGF treatment in E13.5 MEPMs II

Project description:PDGF and FGF treatment in E13.5 MEPMs. 4 hr PDGF treated MEPMs (3 replicates), 4 hr FGF treated MEPMs (3 replicates), 1 hr PDGF + PD325901 treated MEPMs (2 replicates), 4 hr PDGF + PD325901 treated MEPMs (2 replicates), 1 hr FGF + PD325901 treated MEPMs (2 replicates), 4 hr FGF + PD325901 treated MEPMs (2 replicates), 1 hr PDGF + LY294002 treated MEPMs (2 replicates), 4 hr PDGF + LY294002 treated MEPMs (2 replicates), 1 hr FGF + LY294002 treated MEPMs (2 replicates), 4 hr FGF + LY294002 treated MEPMs (2 replicates)

2015-05-07 | GSE66484 | GEO

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