Biology subjects

Matern, M. S.

Publications and source records attributed to Matern, M. S..

3 recordsLinked to original sources

bioRxiv2026

Galectin and Myc enable cochlear progenitor expansion in vitro and in vivo

The neonatal cochlear epithelium harbors regenerative capacity, attributable to the transient greater epithelial ridge (GER). After injury, GER cells re-enter the cell cycle, migrate into the damaged organ of Corti, and differentiate into sensory or supporting cells in vivo; in culture, they proliferate to form inner ear organoids. The mechanisms underlying this competence remain unclear. Here, we generated organoids from mouse GER cells and performed single-cell transcriptomics at organoid initiation. Analysis revealed extracellular matrix reorganization with prominent involvement of galectins. Pharmacological inhibition reduced organoid growth, whereas overexpression of galectin-1 or Myc enhanced growth, identifying both factors as regulators of cochlear progenitor expansion. Moreover, Myc overexpression conferred organoid-forming capacity in post-neonatal cochlear epithelial cells after hearing onset, thereby extending the time window for regenerative competence. In vivo, organ of Corti ablation induced galectin-1 upregulation and GER proliferation, suppressed by galectin-1 blockade, establishing a model to rekindle proliferative potential in mature cochlear cells.

neuroscience↗

bioRxiv2020

gEAR: gene Expression Analysis Resource portal for community-driven, multi-omic data exploration

The gEAR portal (gene Expression Analysis Resource, umgear.org) is an open access community-driven tool for multi-omic and multi-species data visualization, analysis and sharing. The gEAR supports visualization of multiple RNA-seq data types (bulk, sorted, single cell/nucleus) and epigenomics data, from multiple species, time points and tissues in a single-page, user-friendly browsable format. An integrated scRNA-seq workbench provides access to raw data of scRNA-seq datasets for de novo analysis, as well as marker-gene and cluster comparisons of pre-assigned clusters. Users can upload, view, analyze and privately share their own data in the context of previously published datasets. Short, permanent URLs can be generated for dissemination of individual or collections of datasets in published manuscripts. While the gEAR is currently curated for auditory research with over 90 high-value datasets organized in thematic profiles, the gEAR also supports the BRAIN initiative (via nemoanalytics.org) and is easily adaptable for other research domains.

bioinformatics↗

bioRxiv2018

Genomic knockout of alms1 in zebrafish recapitulates Alstrom syndrome and provides insight into metabolic phenotypes

SCIENTIFIC ABSTRACTAlstrom syndrome is an autosomal recessive obesity ciliopathy caused by loss-of-function mutations in the ALMS1 gene. In addition to multi-organ dysfunction, such as cardiomyopathy, retinal degeneration, and renal dysfunction, the disorder is characterized by high rates of obesity, insulin resistance and early onset type 2 diabetes mellitus (T2DM). To investigate mechanisms linking disease phenotypes we generated a loss-of-function deletion of alms1 in the zebrafish using CRISPR/Cas9. We demonstrate conserved phenotypic effects including cardiac defects, retinal degeneration, and metabolic deficits that included propensity for obesity and fatty livers in addition to hyperinsulinemia and glucose response defects. Gene expression changes in {beta}-cells isolated from alms1-/- mutants revealed changes consistent with insulin hyper-secretion and glucose sensing failure, which were also identified in cultured murine {beta}-cells lacking Alms1. These data present a zebrafish model to assess etiology and new secretory pathway defects underlying Alstrom syndrome-associated metabolic phenotypes. Given the hyperinsulinemia and reduced glucose sensitivity in these animals we also propose the alms1 loss-of-function mutant as a monogenic model for studying T2DM phenotypes.\n\nAUTHOR SUMMARYThese data comprise a thorough characterization of a zebrafish model of Alstrom syndrome, a human obesity syndrome caused by loss-of-function deletions in a single gene, ALMS1. The high rates of obesity and insulin resistance found in these patients suggest this disorder as a single-gene model for Type 2 Diabetes Mellitus (T2DM), a disorder caused by a variety of environmental and genetic factors in the general population. We identify a propensity for obesity, excess lipid storage, loss of {beta}-cells in islets, and hyperinsulinemia in larval and adult stages of zebrafish alms1 mutants. We isolated {beta}-cells from the alms1 mutants and compared the gene expression profiles from RNASeq datasets to identify molecular pathways that may contribute to the loss of {beta}-cells and hyperinsulinemia. The increase in genes implicated in generalized pancreatic secretion, insulin secretion, and glucose transport suggest potential {beta}-cell exhaustion as a source of {beta}-cell loss and excess larval insulin. We propose this mutant as a new genetic tool for understanding the metabolic failures found in Type 2 Diabetes Mellitus.

genetics↗