Description
The naked mole-rat (Heterocephalus glaber, NM-R) is an extremophilic rodent with unusual physiological features such as long lifespan, poikilothermy and poor thermoregulation ability. To date, the function of brown adipose tissue (BAT) in NM-R remains unclear. Our aim is to uncover the mechanism(s) regulating the function(s) of the interscapular BAT (iBAT) of NM-R using bulk and snRNA sequencing.
Morphology and histology of NM-R iBAT resemble those of beige adipose tissue. To clarify this hypothesis, we characterized the cellular landscape of NM-R iBAT using snRNAseq analysis. NM-R iBAT exhibited two major cell types, the largest of which consists of adipocytes divided into 4 clusters. The second major cell type, the progenitor compartment, is composed of 3 clusters. The characterization of these clusters allowed to distinguish between white, brown and highly activated brown adipocytes.
We then performed bulk RNA-seq study on iBAT from NM-R (21 months) maintained at 30°C and on iBAT from adult mice kept at either 22°C or 30°C (thermoneutral mice, TM) to identify molecular signaling pathways specific to NM-R iBAT. A global comparison of the transcriptomes revealed significant differences between the two species, as shown by the principal component analysis, while temperature had little effect on gene expression. Differential expression analysis showed that mRNA levels of the key players in thermogenesis, Ucp1 and Trpm8, were upregulated in NM-R iBAT compared to iBAT from mice kept under both temperature conditions. As expected, Ucp1 mRNA was lower in TM mice than in mice kept at 22°C. Interestingly, mRNA levels of molecules of the BAT secretome and regulating sympathetic innervation at the adipose tissue interface were found to be deregulated in NM-R iBAT compared to mice iBAT.
Further characterization of these cell types and of the secretome of NM-R iBAT should allow us to better understand the neuronal regulation of thermogenesis and the function of NM-R iBAT.
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