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Cherian, C. M.

Publications and source records attributed to Cherian, C. M..

3 recordsLinked to original sources

Cell type specific allometry controls sex-differences in Drosophila body size

Species and sex-specific differences in organ size are fundamental features of animal biology, yet the mechanisms that drive these differences remain debated. Adult female Drosophila are larger than males. While most organs are present across both sexes, the underlying mechanisms driving sex-specific organ and body size scaling of Drosophila remain unclear. Using single-nucleus transcriptomes from the Fly Cell Atlas, combined with experimental validation, we show that different Drosophila organs scale through distinct strategies, including cell size, cell number, or a combination of both, in an allometric rather than uniform manner. Larger female flight muscles develop from more myoblasts than in males, while cardiomyocyte numbers are the same despite forming a larger heart in females. Female fat body cells are larger and express more ribosomal protein-coding mRNAs, supporting increased cell size. In contrast, males have a greater number of fat body cells. Together, this sex-specific allometry in cell size and number define the cellular basis for differences in body and organ size between sexes in Drosophila. By uncovering how a conserved developmental system produces sex-specific proportions through distinct cellular strategies, our work offers a framework for dissecting sex differences in other species and systems.

cell biology↗

Neuronal lipid droplets play a conserved and sex-biased role in maintaining whole-body energy homeostasis

ABSTRACTLipids are essential for neuron development and physiology. Yet, the central hubs that coordinate lipid supply and demand in neurons remain unclear. Here, we combine invertebrate and vertebrate models to establish the presence and functional significance of neuronal lipid droplets (LD) in vivo. We find that LD are normally present in neurons in a non-uniform distribution across the brain, and demonstrate triglyceride metabolism enzymes and lipid droplet-associated proteins control neuronal LD formation through both canonical and recently-discovered pathways. Appropriate LD regulation in neurons has conserved and male-biased effects on whole-body energy homeostasis across flies and mice, specifically neurons that couple environmental cues with energy homeostasis. Mechanistically, LD-derived lipids support neuron function by providing phospholipids to sustain mitochondrial and endoplasmic reticulum homeostasis. Together, our work identifies a conserved role for LD as the organelle that coordinates lipid management in neurons, with implications for our understanding of mechanisms that preserve neuronal lipid homeostasis and function in health and disease. HIGHLIGHTSO_LILipid droplets (LD) normally form in neurons across species Neuronal LD are regulated by a conserved gene network C_LIO_LINeuronal LD regulation plays a conserved and sex-biased role in maintaining energy homeostasis C_LIO_LILD regulation supports ER and mitochondrial function in hunger-activated neurons C_LI GRAPHICAL ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=200 SRC="FIGDIR/small/613929v1_ufig1.gif" ALT="Figure 1"> View larger version (54K): org.highwire.dtl.DTLVardef@1936e92org.highwire.dtl.DTLVardef@40478aorg.highwire.dtl.DTLVardef@18d5faorg.highwire.dtl.DTLVardef@882ee9_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗

Consideration of sex as a biological variable in diabetes research across twenty years

Sex differences exist in the risk of developing both type 1 and type 2 diabetes, and in the risk of developing diabetes-associated complications. Sex differences in glucose homeostasis, islet and {beta} cell biology, and peripheral insulin sensitivity have also been reported in multiple animals. To determine the degree to which biological sex has been addressed in published literature related to diabetes and insulin biology, we developed a scoring system to assess the inclusion of biological sex in papers related to these topics. We scored manuscripts published in Diabetes, published by the American Diabetes Association, as this journal focuses on diabetes and diabetes-related research. We scored papers published across three years within a 20-year period (1999, 2009, 2019), a timeframe that spans the introduction of funding agency and journal policies to improve the consideration of biological sex as a variable. Our analysis shows fewer than 15% of papers used sex-based analysis in even one figure across all study years, a trend that was reproduced across journal-defined categories of diabetes research (e.g., islet studies, signal transduction). Single-sex studies accounted for approximately 40% of all manuscripts, of which >87% used male subjects only. While we observed a modest increase in the overall inclusion of sex as a biological variable during our study period, our results highlight significant opportunities to improve consideration of sex as a biological variable in diabetes research. In particular, we show that journal policies represent one way to promote better consideration of biological sex as a variable. In the long term, improved practices will reveal sex-specific mechanisms underlying diabetes risk and complications, generating insights to support the development of sex-informed prevention and treatment strategies.

scientific communication and education↗