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A stably self-renewing adult blood-derived induced neural stem cell exhibiting patternability and epigenetic rejuvenation

ABSTRACT: A stably self-renewing adult blood-derived induced neural stem cell exhibiting patternability and epigenetic rejuvenation

PROVIDER: PRJNA483024 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR7608380.fastq.gz	Fastqsanger.gz
	SRR7608390.fastq.gz	Fastqsanger.gz
	SRR7608381.fastq.gz	Fastqsanger.gz
	SRR7608391.fastq.gz	Fastqsanger.gz
	SRR7608382.fastq.gz	Fastqsanger.gz

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A stably self-renewing adult blood-derived induced neural stem cell exhibiting patternability and epigenetic rejuvenation

Project description:A stably self-renewing adult blood-derived induced neural stem cell exhibiting patternability and epigenetic rejuvenation

| PRJNA483024 | ENA

A stably self-renewing adult blood-derived induced neural stem cell exhibiting patternability and epigenetic rejuvenation

Project description:Recent reports suggest that induced neurons (iNs), but not induced pluripotent stem cell (iPSC)-derived neurons largely preserve age-associated traits. Here we report on the extent of preserved epigenetic and transcriptional aging signatures in directly converted induced neural stem cells (iNSCs). Employing restricted and integration-free expression of SOX2 and c-MYC we generate a fully functional, bona fide NSC population from adult blood cells that remains highly responsive to regional patterning cues. Upon conversion, low passage iNSCs display a profound loss of age-related DNA methylation signatures, which further erode across extended passaging, thereby approximating the DNA methylation age of isogenic iPSC-derived neural precursors. This epigenetic rejuvenation is accompanied by a lack of age-associated transcriptional signatures and absence of cellular aging hallmarks. We find iNSCs to be competent for modeling pathological protein aggregation and for neurotransplantation, depicting blood-to-NSC conversion as a rapid alternative route for both disease modeling and neuroregeneration.

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A stably self-renewing adult blood-derived induced neural stem cell exhibiting patternability and epigenetic rejuvenation.

Project description:Recent reports suggest that induced neurons (iNs), but not induced pluripotent stem cell (iPSC)-derived neurons, largely preserve age-associated traits. Here, we report on the extent of preserved epigenetic and transcriptional aging signatures in directly converted induced neural stem cells (iNSCs). Employing restricted and integration-free expression of SOX2 and c-MYC, we generated a fully functional, bona fide NSC population from adult blood cells that remains highly responsive to regional patterning cues. Upon conversion, low passage iNSCs display a profound loss of age-related DNA methylation signatures, which further erode across extended passaging, thereby approximating the DNA methylation age of isogenic iPSC-derived neural precursors. This epigenetic rejuvenation is accompanied by a lack of age-associated transcriptional signatures and absence of cellular aging hallmarks. We find iNSCs to be competent for modeling pathological protein aggregation and for neurotransplantation, depicting blood-to-NSC conversion as a rapid alternative route for both disease modeling and neuroregeneration.

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Laminin111-based defined culture promoting self-renewing human pluripotent stem cells exhibiting properties of early post-implantation epiblast cells [LN_hPSC_RRBS]

Project description:In our study we sought to develop cultures highly enriched for self-renewing human pluripotent stem cells (hPSCs) with an early post-implantation phenotype, capturing the formative pluripotency phase in vitro. Our results demonstrate that hPSCs cultured on LN111 in defined conditions (LN-hPSCs) generate cultures highly enriched for genetically stable, self-renewing hPSCs exhibiting properties similar to the early-post implantation epiblast, including competence to give rise to the germ cell lineage. To analyze the global transcriptome of LN-hPSCs in comparison with conventional/primed and naive hPSCs, we performed RNA-seq of the three hPSC lines cultured under LN, primed, and naïve conditions.

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Laminin111-based defined culture promoting self-renewing human pluripotent stem cells exhibiting properties of early post-implantation epiblast cells [Bulk_RNA_Seq]

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