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Single cell transcriptomics of yound and aged naked mole-rat (NMR) epidermal cells

ABSTRACT: Single cell transcriptomics of yound and aged naked mole-rat (NMR) epidermal cells

PROVIDER: PRJNA640800 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR12060384_1.fastq.gz	Fastqsanger.gz
	SRR12060384_2.fastq.gz	Fastqsanger.gz
	SRR12060385_1.fastq.gz	Fastqsanger.gz
	SRR12060385_2.fastq.gz	Fastqsanger.gz
	SRR12060386_1.fastq.gz	Fastqsanger.gz

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Single cell transcriptomics of yound and aged naked mole-rat (NMR) epidermal cells

Project description:Study the global transcriptional heterogeneity of young and aged NMR epidermis using scRNA-seq,

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Project description:The role of CD44 in naked-mole rats (NMR) oligodendrocyte progenitor cells (OPCs) were evaluated by comparing the transcriptome of control and CD44-knockdown NMR OPCs.

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Project description:This study compares the transcriptional response to hypoxia in liver of the hypoxia-tolerant naked mole rat (NMR) and the hypoxia-sensitive rat.

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Project description:Transcriptome of long-lived naked-mole rat (NMR) oligodendrocyte progenitor cells (OPCs) were compared with OPCs of other species.

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Age-associated changes in the skin transcriptome in Naked mole-rats

Project description:Naked mole rats (NMRs, Heterocephalus glaber) are long-lived mammals that possess a natural resistance to cancer and other age-related pathologies, maintaining a healthy life span for >30 years. We report application of RNAseq technology to analyze changes in the skin transcriptome of NMRs during aging. RNAseq analyses reveal that the transcript levels of several longevity-associated (Igfbp3, Igf2bp3, Ing2) and tumor-suppressor genes (Btg2, Cdkn1a, Cdkn2c, Dnmt3a, Hic1, Socs3, Sfrp1, Sfrp5, Thbs1, Tsc1, Zfp36) are increased in aged versus young NMR skin. Overall, these data suggest that specific features in the NMR skin aging transcriptome might contribute to the resistance of NMRs to spontaneous skin carcinogenesis and provide a platform for further investigations of NMRs as a model organism for studying the biology and disease resistance of human skin.

2022-04-26 | GSE200736 | GEO

Transformation of Naked Mole-Rat Cells

Project description:The naked mole-rat (NMR), Heterocephalus glaber, is a mouse-sized subterranean rodent native to East Africa. Research on NMRs is intensifying in an effort to gain leverage from their unusual physiology, long-life span and cancer resistance for the development of new theraputics. Few studies have attempted to explain the reasons behind the NMR’s cancer resistance, but most prominently Tian et al. reported that NMR cells produce high-molecular weight hyaluronan as a potential cause for the NMR’s cancer resistance. Tian et al. have shown that NMR cells are resistant to transformation by SV40 Large T Antigen (SV40LT) and oncogenic HRAS (HRASG12V), a combination of oncogenes sufficient to transform mouse and rat fibroblasts. We have developed a number of lentiviral vectors to deliver both these oncogenes and generated 106 different cell lines from five different tissues and eleven different NMRs, and report here that contrary to Tian et al.’s observation, NMR cells are susceptible to oncogenic transformation by SV40LT and HRASG12V. Our data thus point to a non-cell autonomous mechanism underlying the remarkable cancer resistance of NMRs. Identifying these non-cell autonomous mechanisms could have significant implications on our understanding of human cancer development.

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Transcriptome sequencing of naked mole rat, Heterocephalus glaber

Project description:Deep sequencing of mRNA from naked mole rat

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Project description:The naked mole rat (NMR), a long-lived and cancer resistant rodent, is highly resistant to hypoxia. Here, using robust cellular models wherein the mouse telomeric protein TRF1 is substituted by the NMR TRF1 or its mutant forms, we show that TRF1 supports maximal glycolytic capacity under low oxygen, shows increased nuclear localization and association with telomeres, and protects telomeres from replicative stress. We pinpoint this evolutionary gain of metabolic function to specific amino acid changes in the homodimerization domain of this protein. We further find that NMR TRF1 accelerates telomere shortening. These findings reveal an evolutionary strategy to adapt telomere biology for metabolic control under an extreme environment.

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Project description:The naked mole-rat (NMR) is an exceptionally long-lived rodent that does not show increased mortality with age, uniquely defining NMR as a demographically non-aging mammal. Here, we performed bisulfite sequencing on over one hundred NMR blood samples differing in age, assessing more than 3 million common CpG sites. We observed an information loss of the NMR methylome during aging suggesting that NMR ages. Unsupervised clustering based on the 758 CpG sites whose methylation level strongly correlate with age suggests an age-related shift of the NMR methylome. We also developed an epigenetic aging clock that accurately predicts the NMR age spread across the genome. Based on the clock, NMRs age much slower than mice and much faster than humans, consistent with their known maximum lifespans. We further found that patterns of age-related methylation changes of aging clock sites in Tert and Prpf19 showed differences between NMRs and mice. Together, the data indicate that NMRs, like other mammals, epigenetically age even in the absence of demographic aging of this species.

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