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Naked mole rat cells show resistance to iPSC reprogramming and signs of more stable epigenome

ABSTRACT: Naked mole rat cells show resistance to iPSC reprogramming and signs of more stable epigenome

PROVIDER: PRJNA326430 | ENA |

REPOSITORIES: ENA

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Naked mole rat cells show resistance to iPSC reprogramming and signs of more stable epigenome

Project description:Naked mole rat (NMR) is a valuable model for aging and cancer research due to its exceptional longevity and resistance to tumorigenesis. In an effort to generate NMR induced pluripotent stem cells (iPSCs) we observed that reprogramming efficiency of NMR fibroblasts in repsonse to OSKM overexpression was drasticaly lower than that of mouse fibroblasts. To understand the cause of NMR resistance to reprogramming we screened for factors that improve reprogramming effciency. We identified that expression of SV40 Large T (LT) dramatically improved reprogramming of NMR fibroblasts. Inactivation of Rb alone, but not p53, was suffcient to improve reprogramming effciency suggesting that NMR chromatin structure is refractory to reprogramming. Analysis of global histone landscape using quantitative mass spectrometry revealed that NMR fibroblasts had higer levels of repressive H3K27 methylation marks, and lower levels of activating H3K27 acetylation mark than the mouse fibroblasts. Furthermore, the NMR cells had lower levels of permissive H2A.Z acetylation marks. ChIP showed that of E-cadherin had repressive H3K9me3 histone mark in the NMR, but was poised with a bivalent H3K4me3/H3K27me3 in the mouse. Expression of LT reduced the levels of H3K9me3 mark on E-cadherin promoter. ATAC-seq revealed that NMR had more open chromatin globally, however, NMR promoters were more closed than mouse promoters. Expression of LT antigen led to massive opening of the NMR promoters including gene promoters required for reprogramming. Cumulatively, these data suggest that NMR has more stable epigenome than mouse, which resists reprogramming and may contribute to NMR longevity and cancer resistance.

2017-06-21 | GSE83585 | GEO

Transcriptome sequencing of naked mole rat, Heterocephalus glaber

Project description:Deep sequencing of mRNA from naked mole rat Analysis of ploy(A)+ RNA of different specimens: brain, kidney, liver from new born , 4 years old , 20 years old and 4 years old hypoxia-exposed naked mole rat

2011-10-12 | E-GEOD-30337 | biostudies-arrayexpress

Transcriptome sequencing of naked mole rat, Heterocephalus glaber

Project description:Deep sequencing of mRNA from naked mole rat

2011-10-12 | GSE30337 | GEO

Single-cell RNA-Sequencing maps the hematopoietic landscape in naked mole-rats [unfractionated LY]

Project description:Naked mole-rats are a mammalian model organism of exceptional longevity. We mapped the T cell developmental landscape in Naked mole-rats and showed

2021-10-15 | GSE185721 | GEO

Postnatal Oogenesis In the Naked Mole Rat

Project description:The goal of this analysis is to compare the transcriptome profile (RNA-seq) along different developmental ages in the naked mole rat ovary

2023-02-21 | GSE139515 | GEO

RNA sequencing of the spleen of naked mole-rat and mouse

Project description:Heathly naked mole-rats kept under normal housing conditions harbor either a small or enlarged spleen. The aim of the study is to compare RNAseq of naked mole-rat (NM-R) small and enlarged spleens between them and to compare them with RNAseq of mouse spleen.

2022-04-06 | GSE179350 | GEO

Naked mole-rat proteomic analysis

Project description:Analysis of the Naked mole-rat proteome relative to mice

2020-12-18 | MSV000086617 | MassIVE

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Naked Mole-Rat transformation

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Bulk RNA-seq datasets of co-injected naked mole rat and human fibroblasts to NSG mice 2022

Project description:To study the tumour-suppressive capabilities of naked mole-rat fibroblasts we subcutaneously co-injected the fibroblasts and human squamous carcinoma cells into the flanks of NSG mice, which lack mature T cells. As controls, we (1) performed the co-injection experiment with mouse fibroblasts, and (2) performed experiments in which we injected human squamous carcinoma cells without mouse or naked mole-rat fibroblasts. To determine how the co-injections with mouse or naked mole-rat fibroblasts affected tumour growth in vivo, we then transcriptionally profiled the human skin tumours.

2023-11-21 | E-MTAB-12455 | biostudies-arrayexpress

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