Project description:Identify shifts in gene expression relevant to torpor phenotypes and recovery following torpor in five tissues of the 13-lined ground squirrel. Sampled tissues and time points overlap with prior hibernation RNA-seq studies in 13-lined ground squirrel and other species, allowing for the analysis of conserved gene expression patterns in torpor.
Project description:Hibernation is a seasonally adaptive strategy that allows hibernators to live through extreme cold condition and was viewed as a highly regulated physiological event. In spite of the profound reduction of blood flow to retina, hibernation causes no lasting retinal injury and hibernators show increased tolerance to ischemic insults during hibernation period. To understand the molecular changes of retina in response to hibernation we applied transcriptomic analysis to explore the changes of gene expression of 13-lined ground squirrel retinas during hibernation.
Project description:Evolutionary adaptation to diurnal vision in ground squirrels has led to the development of a cone-dominant retina, in stark contrast to the rod-dominant retinas of most mammals. The molecular mechanisms driving this shift remain largely unexplored. Here, we perform single-cell RNA sequencing (scRNA-Seq) and chromatin accessibility profiling (scATAC-Seq) across developmental retinal neurogenesis in the 13-lined ground squirrel (13LGS) to uncover the regulatory basis of this adaptation. We find that 13LGS cone photoreceptors arise not only from early-stage neurogenic progenitors, as seen in rod-dominant species like mice, but also from late-stage neurogenic progenitors. This extended period of cone generation is driven by a heterochronic shift in transcription factor expression, with cone-promoting factors such as Onecut2, Pou2f1, and Zic3 remaining active in late-stage progenitors, while cone-differentiation factors Thrb, Rxrg, and Mef2c are expressed precociously in cone specification. Functional analyses reveal that Zic3 and Mef2c promote cone specification, acting through species-specific regulatory elements that drive their expression in late-stage progenitors. These results demonstrate that evolutionary modifications to gene regulatory networks underlie the development of cone-dominant retinas, providing insight into mechanisms of sensory adaptation and potential strategies for cone photoreceptor regeneration in vision disorders.
