Kathrin Kajderowicz Thesis Defense: Genetic Regulators of Cold Tolerance and Torpor Neurons Across Mammals
Description
Date & time: Thursday, April 30th at 12pm
Location (building/room for in-person): Picower Seminar Room 46-3310
Zoom link (hybrid): https://mit.zoom.us/j/98995521378
Talk title: Genetic Regulators of Cold Tolerance and Torpor Neurons Across Mammals
Abstract:
The ability of certain species to profoundly modulate body temperature is a remarkable phenomenon driven by whole-organism mechanisms that regulate the induction of these states, as well as cell-intrinsic properties that allow individual cells to survive extreme temperatures. While prior research has both identified broad neuronal populations capable of inducing torpor-like states and pathways linked to cold-induced cell death, the specific neuronal cell types controlling these states and genetic suppressors of cold-induced cell death remain unknown, preventing the ability to make precise cross-species comparisons. To address these gaps, in Chapter 2 we conducted the first genome-wide CRISPR screen in hibernator cells derived from the Syrian golden hamster, and performed a parallel screen in human cells. We identified GPX4 as a conserved genetic suppressor of cold-induced cell death, validating its role in primary cell lines derived from several homeothermic and heterothermic mammals. In Chapter 3, we utilize single nucleus RNA sequencing datasets integrated with a MERFISH dataset to generate a spatially restricted neuronal atlas of the mouse preoptic area of the hypothalamus (POA), a region previously implicated in thermoregulatory functions cross-species. Using our atlas, we identified a molecularly defined minimal population of glutamatergic Rxfp2-expressing neurons. We demonstrated through functional testing that these neurons are sufficient to induce a profound, torpor-like decrease in body temperature in our newly generated Rxfp2 -Cre transgenic mouse line. Finally, we conduct a preliminary characterization of conserved torpor inducing cell types using our POA mouse atlas integrated with single nucleus RNA sequencing datasets from collected rat, hamster, and marmoset POA samples.