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.
Project description:Naked mole-rat show a strong phenotype of sperm hypo-motility and abnormal morphology. Comparative genomic analyses in our study presenting the telomere-to-telomere genome for the naked mole-rat identified several sperm-gene relaxation and sperm-gene loss events in the NMR. To test the transcriptomic impacts of these gene-loss events, we performed RNA-seq between the sperm of NMR subordinates, ex-subordinates released from suppressive colony cues, and mice. Briefly, only 5-15% of NMR sperm have typical morphology, and only ~7% of those sperm were motile, whereas over 70% of M. musculus sperm are intact and motile There was insufficient motile sperm in the NMR to separate sperm based on motility before RNA-seq. This study was sequenced with sufficient depth to allow for improved sperm-gene annotation. As such, each sample contains over 50 million reads sequenced. In this study, we compared subordinate vs. ex-subordinates in the NMR, as well as all mice vs. all NMRs
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.
Project description:The naked mole-rat (NMR; Heterocephalus glaber) is a eusocial subterranean rodent with a highly unusual set of physiological traits, such as extreme longevity, that has attracted great interest amongst the scientific community. However, the genetic basis of most of these traits has not been elucidated. To facilitate our understanding of the molecular mechanisms underlying NMR physiology and behaviour, we generated a long-read chromosomal-level genome assembly of the NMR. To complement gene annotation and ascertain the organization of an NMR epigenome, we generated a chromatin state map of the female subordinate hypothalamus hypothalamus that included long-range promoter-enhancer interactions. This repository stores the ATAC-seq data used in the chromatin state map. Specifically, this dataset contains female subordinates, male subordinates, female exsubordinates 1 week after colony removal, and male exsubordinates 1 week after colony removal (N=3 per sex and pubertal stage).
Project description:Mammals display wide range of variation in their lifespan. Investigating the molecular networks that distinguish long- from short-lived species has proven useful to identify determinants of longevity. Here, we compared the liver of long-lived naked mole-rats (NMRs) and the phylogenetically closely related, shorter-lived, guinea pigs using an integrated omic approach. We found that NMRs livers display a unique expression pattern of mitochondrial proteins that result in distinct metabolic features of their mitochondria. For instance, we observed a generally reduced respiration rate associated with lower protein levels of respiratory chain components, particularly complex I, and increased capacity to utilize fatty acids. Interestingly, we show that the same molecular networks are affected during aging in both NMR and humans, supporting a direct link to the extraordinary longevity of both species. Finally, we identified a novel longevity pathway and validated it experimentally in the nematode C. elegans.
Project description:The naked mole-rat (NMR; Heterocephalus glaber) is a eusocial subterranean rodent with a highly unusual set of physiological traits, such as extreme longevity, that has attracted great interest amongst the scientific community. However, the genetic basis of most of these traits has not been elucidated. To facilitate our understanding of the molecular mechanisms underlying NMR physiology and behaviour, we generated a long-read chromosomal-level genome assembly of the NMR. To complement gene annotation and ascertain the organization of an NMR epigenome, we generated a chromatin state map of the female subordinate hypothalamus hypothalamus that included long-range promoter-enhancer interactions. This repository stores the ChIP-seq data used in the chromatin state map (H3K4me3, H3K4me2, H3K27Ac, H3K27me3, H3K36me3, H3K9me3, CTCF-whole-brain), and promoter and enhancer mapping of male subordinate hypothalamus samples (H3K4me3, H3K4me2).
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.
Project description:This data contributes to a telomere-to-telomere genome assembly and annotation of the naked mole-rat, Heterocephalus glaber. To epigenetically annotate centromeres, we performed CENPA ChIP-seq experiments in the male subordinate NMR livers. To ensure antibody quality, as this was the first time CENPA ChIP-seq was performed in the NMR, we performed H3K27Ac and CENPA ChIP-seq experiments on a TeloHAOEC cell line.
Project description:This data contributes to a telomere-to-telomere genome assembly and annotation of the naked mole-rat, Heterocephalus glaber. To epigenetically annotate centromeres, we performed CENPA ChIP-seq experiments in the male subordinate NMR livers. These experiments included an Input control, and a H3K27Ac ChIP-seq experiment to annotate active enhancers and ensure hat the ChIP-seq experiment with antibodies performed as expected.
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.