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Partial reprogramming restores youthful gene expression through transient suppression of cell identity

ABSTRACT: Partial reprogramming restores youthful gene expression through transient suppression of cell identity

PROVIDER: PRJNA735380 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR14740030_1.fastq.gz	Fastqsanger.gz
	SRR14740030_2.fastq.gz	Fastqsanger.gz
	SRR14740031_1.fastq.gz	Fastqsanger.gz
	SRR14740031_2.fastq.gz	Fastqsanger.gz
	SRR14740032_1.fastq.gz	Fastqsanger.gz

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Partial reprogramming restores youthful gene expression through transient suppression of cell identity

Project description:Transient induction of pluripotent reprogramming factors has been reported to reverse some features of aging in mammalian cells and tissues. However, the impact of transient reprogramming on somatic cell identity programs and the necessity of individual pluripotency factors remain unknown. Here, we mapped trajectories of transient reprogramming in young and aged cells from multiple murine cell types using single cell transcriptomics to address these questions. We found that transient reprogramming restored youthful gene expression in adipogenic cells and mesenchymal stem cells but also temporarily suppressed somatic cell identity programs. We further screened Yamanaka Factor subsets and found that many combinations had an impact on aging gene expression and suppressed somatic identity, but that these effects were not tightly entangled. We also found that a transient reprogramming approach inspired by amphibian regeneration restored youthful gene expression in aged myogenic cells. Our results suggest that transient pluripotent reprogramming poses a neoplastic risk, but that restoration of youthful gene expression can be achieved with alternative strategies.

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Project description:Partial reprogramming by expression of reprogramming factors (Oct4, Sox2, Klf4 and cMyc) for short periods of time restores a youthful epigenetic signature to aging cells and extends the lifespan of a premature aging mouse model. However, the effects of longer-term partial reprogramming in physiologically aging wild-type mice are unknown. Here, we have performed various long-term partial reprogramming regimens, including different onset timings, during physiological aging in different mouse strains. n=239 tissues from mice. The study involves different conditions (treated and untreated samples) and leads to 7 groups: 1) Black6 mouse +Doxocycline 2) 4 factor mouse+1 month of Doxocycline. 3) 4F mice+7month of Dox 4) 4F+10 months of Dox 5) 4F mice which are relatively old 6) B6 mice that are relatively old 7) 4F mice which are relatively young.

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