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Dynamics of Telomere Rejuvenation During Chemical Induction to Pluripotent Stem Cells

ABSTRACT: Dynamics of Telomere Rejuvenation During Chemical Induction to Pluripotent Stem Cells

PROVIDER: PRJNA454471 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR7089060_1.fastq.gz	Fastqsanger.gz
	SRR7089060_2.fastq.gz	Fastqsanger.gz
	SRR7089070_1.fastq.gz	Fastqsanger.gz
	SRR7089070_2.fastq.gz	Fastqsanger.gz
	SRR7089051_1.fastq.gz	Fastqsanger.gz

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Dynamics of Telomere Rejuvenation During Chemical Induction to Pluripotent Stem Cells

Project description:Chemical induced pluripotent stem cells (CiPSCs) have been successfully achieved and may provide an alternative and attractive source for stem cell-based therapy. Sufficient telomere lengths are critical for unlimited self-renewal and genomic stability of pluripotent stem cells. Dynamics of telomere reprogramming and whether and how telomeres are sufficiently elongated in the CiPSCs have remained to be understood. We show that CiPSCs acquire telomere lengthening with increasing passages after clonal formation. Both telomerase activity and recombination-based mechanisms are involved in the telomere elongation. Telomere lengths strongly indicate the degree of reprogramming, pluripotency and differentiation capacity of CiPSCs. Nevertheless, telomere damage and shortening occur at late stage of lengthy induction, limiting CiPSC formation. Recombination mechanism is not activated during induction until CiPSC clonal formation and passages. We find that histone crotonylation induced by crotonic acid can activate two-cell genes including Zscan4, alleviate telomere damage and shortening during induction and promote CiPSC generation. Moreover, crotonylation decreases abundance of heterochromatic H3K9me3 and HP1a at subtelomeres and Zscan4 loci. Taken together, telomere rejuvenation links to reprogramming and pluripotency of CiPSCs. Crotonylation facilitates telomere maintenance and enhances chemical induced reprogramming to pluripotency.

2018-05-01 | GSE113921 | GEO

Dynamics of Telomere Rejuvenation during Chemical Induction to Pluripotent Stem Cells.

Project description:Chemically induced pluripotent stem cells (CiPSCs) may provide an alternative and attractive source for stem cell-based therapy. Sufficient telomere lengths are critical for unlimited self-renewal and genomic stability of pluripotent stem cells. Dynamics and mechanisms of telomere reprogramming of CiPSCs remain elusive. We show that CiPSCs acquire telomere lengthening with increasing passages after clonal formation. Both telomerase activity and recombination-based mechanisms are involved in the telomere elongation. Telomere lengths strongly indicate the degree of reprogramming, pluripotency, and differentiation capacity of CiPSCs. Nevertheless, telomere damage and shortening occur at a late stage of lengthy induction, limiting CiPSC formation. We find that histone crotonylation induced by crotonic acid can activate two-cell genes, including Zscan4; maintain telomeres; and promote CiPSC generation. Crotonylation decreases the abundance of heterochromatic H3K9me3 and HP1α at subtelomeres and Zscan4 loci. Taken together, telomere rejuvenation links to reprogramming and pluripotency of CiPSCs. Crotonylation facilitates telomere maintenance and enhances chemically induced reprogramming to pluripotency.

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Chromatin Accessibility Dynamics during Chemical Induction of Pluripotency

Project description:Chromatin Accessibility Dynamics during Chemical Induction of Pluripotency

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Chromatin Accessibility Dynamics during Chemical Induction of Pluripotency [RNA-seq]

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Chromatin Accessibility Dynamics during Chemical Induction of Pluripotency [ChIP-seq]

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Chromatin Accessibility Dynamics during Chemical Induction of Pluripotency [ATAC-Seq]

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Multi-omics characterization of partial chemical reprogramming reveals evidence of cell rejuvenation

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Project description:We examined how each chemical contributed to hepatocyte revitalization by removing each component of the 5C induction cocktail individually. We then compared deach chemical contributed to hepatocyte revitalization by removing each component of the 5C induction cocktail individually

2023-11-21 | GSE233082 | GEO

Chromatin Accessibility Dynamics during Chemical Induction of Pluripotency [RNA-seq]

Project description:Chemical induction of pluripotency (CIP) is an ideal way to reprogram cell fate, but remains poorly understood. Here we report the development of an efficient CIP protocol and the chromatin accessibility dynamics (CAD) during CIP by ATAC-seq. CIP first reorganizes the somatic genome to an intermediate state that must be resolved by primarily closing loci opened earlier before reaching a pluripotent state with gradual opening of loci enriched with motifs for the OCT/SOX/KLF families. Bromodeoxyuridine, a critical ingredient of CIP, is responsible for both closing and opening critical loci, at least in part by preventing the opening of loci enriched with motifs for the AP1 family and facilitating the opening of loci enriched with SOX/KLF/GATA motifs. Our studies provide the first link between small molecules and nuclear architecture in the context of cell fate decisions.

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