Biology subjects

Meisel, R.

Publications and source records attributed to Meisel, R..

6 recordsLinked to original sources

bioRxiv2026

Common and Sex-Biased Muscle Transcriptomic Aging Signatures Across Diverse Species

Sex differences in lifespan are widespread yet inconsistent across the animal kingdom. In mammals, XX females outlive XY males in over 60% of species, while this pattern reverses in birds, where ZZ males have a higher life expectancy. These sex differences raise the question of whether sex-biased aging biomarkers (age-associated molecular signatures that reflect biological aging processes) can be identified based on transcriptomic data and whether such markers are shared across taxa. To identify sex-biased aging biomarkers, we analyzed sex-specific skeletal muscle transcriptomes (RNA-seq) from young and old individuals of six species spanning major evolutionary lineages. Four female-biased and 18 male-biased aging biomarkers were identified across all species. Three shared aging biomarkers were also identified in both sexes of all species: Na Channel, Heat Shock Protein 70 (HSP70), and Secreted Protein Acidic and Rich in Cysteine (SPARC). Particularly, age-associated changes in the HSP70 family are suggestive of a shared decline in proteostasis, a hallmark of aging observed across both model and non-model organisms. Furthermore, using an Ornstein-Uhlenbeck (OU) model applied to orthogroup phylogenies, we identified lineage- and sex-dependent expression shifts in shared aging biomarkers. In addition, sex-biased orthogroups revealed age-associated alterations in muscle structure and function in females, whereas mitochondrial and metabolic pathways were predominantly changed in males, indicating divergent mechanisms in muscle aging between sexes. Together, these findings identified a set of transcriptional aging signatures, both shared and sex-biased, that are detectable across diverse evolutionary lineages, providing insight into shared and divergent molecular mechanisms underlying aging.

genomics↗

bioRxiv2026

Genotype and environmental effects shape the house fly microbiome (Musca domestica)

Animal-associated bacteria (microbiomes) can have important effects on host phenotypes and fitness. Microbiomes can also vary across individuals in ways that depend on host genotype and environment. Temperature is an especially important environmental factor that can affect the microbiome in a way that depends on host genotype and affects organismal fitness. Thermal stress, in particular, can have dramatic effects on animal microbiomes, including dysbiosis and immune dysregulation. However, most previous work on extreme temperature effects has focused on heat stress. To investigate how low temperatures affect the microbiome of a warm-adapted animal, we characterized the bacterial communities associated with house fly (Musca domestica) males raised at cool (18{degrees}C) and warm (29{degrees}C) temperatures. We sampled two distinct genotypes in these experimental flies, each of which is associated with a particular thermal environment (warm or cool). We contrasted our experimental results with the microbiomes we characterized in wild house flies from two collection sites with different large animals present. We found that temperature has a much stronger effect on the house fly microbiome than the host genotype in our experimental flies. Consistent with the strong environmental effects in our experiment, we found that wild house fly microbiomes differed between the two collection sites. Despite these environmental effects on the house fly microbiome, we did not detect evidence for dysbiosis associated with either cool or warm temperatures. We therefore conclude that the environment has more of an effect on the house fly microbiome than host genotype, but dysbiosis does not occur within the temperature range we considered.

ecology↗

bioRxiv2025

Comparative Transcriptomic Analysis of Embryonic Stem Cells (ESCs) across Mammalian Species

Pluripotency, the ability of cells to self-renew and differentiate into all the cell types in an animals body, is vital for mammalian early development. This study presented a comprehensive comparative transcriptomic analysis of embryonic stem cells across multiple mammalian species, defining their progression through expanded/extended, naive, formative, and primed pluripotency states. Our findings revealed both conserved and species-specific mechanisms underlying pluripotency regulation. We also emphasized the limitations of existing state-specific markers and their limited cross-species applicability, while identifying de novo pluripotency markers that can inform future research. Despite variability in gene expression dynamics, gene co-expression networks showed remarkable conservation across species. Among pluripotency states, the primed state demonstrated the highest conservation, evidenced by shared markers, preserved gene networks, and stronger selective pressures acting on its genes. These findings provide critical insights into the evolution and regulation of pluripotency, laying a foundation for refining stem cell models to enhance their translational potential in regenerative medicine, agriculture, and conservation biology.

genomics↗

bioRxiv2024

HCM-associated mutations in MYH6/7 drive pathologic expression of TGF-β1 in cardiomyocytes within weeks of developmental specification

Hypertrophic cardiomyopathy (HCM) is characterized by myocyte hypertrophy, sarcomere disarray, and myocardial fibrosis, leading to significant morbidity and mortality. As the most common inherited cardiomyopathy, HCM largely results from mutations in sarcomeric protein genes. Current treatments for HCM primarily focus on alleviating late-stage symptoms, with a critical gap in the detailed understanding of early-stage deficiencies that drive disease progression. We recently showed, in monolayers of cardiomyocytes derived from human induced pluripotent stem cells (hiPSCs) with MYH7 R723C and MYH6 R725C mutations, altered expression of several extracellular matrix (ECM)-related genes with associated defects in cardiomyocyte-ECM adhesion. To better evaluate the cardiomyocyte-ECM interface and pathological ECM dynamics in early-stage HCM, here we adopted a 3D engineered heart tissue (EHT) model containing both cardiomyocytes and fibroblasts, the primary contributor to ECM remodeling. Mutant EHTs showed aberrant cardiomyocyte distribution, augmented calcium handling, and force generation compared to controls. Altered proteoglycan deposition and increased phosphorylated focal adhesion kinase (pFAK) further indicated changes in ECM composition and connectivity. Elevated transforming growth factor beta-1 (TGF-{beta}1) secretion and a higher proportion of activated fibroblasts were identified in mutant EHTs, along with sustained TGF-{beta}1 transcription specifically in mutant cardiomyocytes. Remarkably, blocking TGF-{beta}1 receptor signaling reduced fibroblast activation and contraction force to control levels. This study underscores the early interplay of mutant hiPSC-CMs with fibroblasts, wherein mutant cardiomyocytes initiate fibroblast activation via TGF-{beta}1 overexpression, independent of the immune system. These findings provide a promising foundation for developing and implementing novel strategies to treat HCM well before the manifestation of clinically detectable fibrosis and cardiac dysfunction.

bioengineering↗

bioRxiv2019

High rate of sex chromosome turnover in muscid flies

Sex chromosomes and sex determining genes can evolve fast, with the sex-linked chromosomes often differing between closely related species. A substantial body of population genetics theory has been developed and tested to explain the rapid evolution of sex chromosomes and sex determination. However, we do not know why the sex-linked chromosomes differ between some species pairs yet are relatively conserved in other taxa. Addressing this question will require comparing closely related taxa with conserved and divergent sex chromosomes and sex determination systems to identify biological features that could explain these rate differences. Cytological karyotypes suggest that muscid flies (e.g., house fly) and blow flies are such a taxonomic pair. The sex chromosomes appear to differ across muscid species, whereas they are highly conserved across blow flies. Despite the cytological evidence, we do not know the extent to which muscid sex chromosomes are independently derived along different evolutionary lineages. To address that question, we used genomic data to identify young sex chromosomes in two closely related muscid species, horn fly (Haematobia irritans) and stable fly (Stomoxys calcitrans). We provide evidence that the nascent sex chromosomes of horn fly and stable fly were derived independently from each other and from the young sex chromosomes of the closely related house fly (Musca domestica). We present three different scenarios that could have given rise to the sex chromosomes of horn fly and stable fly, and we describe how the scenarios could be distinguished. Distinguishing between these scenarios in future work could help to identify features of muscid genomes that promote sex chromosome divergence.

evolutionary biology↗

bioRxiv2017

Genes relocated between Drosophila chromosomes evolve under selection pressures different from canonical dispersed duplicates

Gene duplication creates a second copy of a gene either in tandem to the ancestral locus or dispersed to another chromosomal location. When the ancestral copy of a dispersed duplicate is lost from the genome, it creates the appearance that the gene was \"relocated\" from the ancestral locus to the derived location. Gene relocations may be as common as canonical dispersed duplications in which both the ancestral and derived copies are retained. Relocated genes appear to be under more selective constraints than the derived copies of canonical duplications, and they are possibly as conserved as single-copy non-relocated genes. To test this hypothesis, we combined comparative genomics, population genetics, gene expression, and functional analyses to assess the selection pressures acting on relocated, duplicated, and non-relocated single-copy genes in Drosophila genomes. We find that relocated genes evolve faster than single-copy non-relocated genes, and there is no evidence that this faster evolution is driven by positive selection. In addition, relocated genes are less essential for viability and male fertility than single-copy non-relocated genes, suggesting that relocated genes evolve fast because of relaxed selective constraints. However, relocated genes evolve slower than the derived copies of canonical dispersed duplicated genes. We therefore conclude that relocated genes are under more selective constraints than canonical duplicates, but are not as conserved as single-copy non-relocated genes.

genetics↗