Evidence map›Paper›PMID 31304203›Full record

ArticleRegenerative therapy2019

Increased error-free DNA repair gene expression through reprogramming in human iPS cells.

Yasuhide Yoshimura

Abstract read
In one paragraph

Article in Regenerative therapy, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

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2 · The registry

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3 · Its place in the literature

Who cites it

3 citing papers in PubMed.

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4 · The record

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5 · Who and what money

Authors and funding

1 author.

Yasuhide YoshimuraDivision of Gene Therapy Science, Department of Genome Biology, Graduate School of Medicine, Osaka University, Address: 2-2 Yamada-oka, Suita, Osaka 565-0871, Japan.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

introductionMany studies have reported that human-induced pluripotent stem (hiPS)/embryonic stem (hES) cells have an exceptional ability to repair damaged DNA. Moreover, unlike differentiated cells, hES cells have features and mechanisms such as apoptosis-prone mitochondria, which prevent any changes in genetic information caused by DNA damage to be transmitted to their descendants. Type-A (dark) spermatogonia and cancer stem cells are thought to be dormant. However, hiPS/hES cells, the so-called stem cells used in regenerative medicine, generally have a high proliferative capacity. This suggests that in these cells, oxidative DNA damage associated with vigorous proliferation and DNA scission associated with replication occur frequently. Although pluripotency according to change of genomic structure is well studied, the change of DNA repair through reprogramming has not been well studied.

methodsWe analyzed the expression of DNA repair-related genes in hiPS cells using microarray and western blotting analyses and assessed changes in PARP activity through reprogramming.

resultsThrough reprogramming, hiPS cells were found to upregulate poly (ADP-ribose) polymerase (PARP) activity and genes regulating homologous recombination (HR). Simultaneously, the expression level of genes involved in non-homologous end joining (NHEJ) was not high, suggesting that at least at the gene expression level, frequently occurring DNA scission is preferentially dealt with via HR instead of NHEJ. Also, reflecting the high proliferative activity, genes related to mismatch repair (MMR) were upregulated through reprogramming. Conversely, error-prone polymerase was downregulated through reprogramming. These are also likely to be the mechanisms preventing changes in genetic information.

conclusionsHigh PARP activity and HR-related gene expression in hiPS cells were achieved through reprogramming and likely facilitate precise genome editing in these cells in exchange for a high possibility of cell death.

Indexed as

BLMBLM, the gene defective in Bloom's syndromeDNA repairHDF, human dermal fibroblastHomologous recombinationiPS, induced pluripotent stemMSC, mesenchymal stromal cellPARPPARP, poly (ADP-ribose) polymeraseRAD51ReprogrammingROS, Reactive Oxygen Species

Identifiers

PMID31304203
PMCPMC6606834

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.