Biology subjects

Urman, M. A.

Publications and source records attributed to Urman, M. A..

3 recordsLinked to original sources

bioRxiv2025

Comprehensive comparative analysis of the effects of temperature on the Notch signaling response in vivo

Temperature is a critical factor that modulates cellular metabolism and stem cell regulation. Despite extensive studies, the influence of temperature on stem cell regulation via Notch signaling has been limited to studies relying on studies that involve indirect readouts to Notch activation. This study systematically analyzes the effects of temperature on the Notch signaling transcriptional response at the chromosomal, cellular, and tissue levels. Using complementary direct Notch readouts, we demonstrate that Notch activation remains largely unchanged across temperatures, suggesting the presence of temperature-compensatory mechanisms that maintain robust Notch activation. Notch transcriptional activity readouts, however, increased with temperature, indicating that elevated temperatures may enhance Notch transcriptional activity at the chromosomal level. These findings provide a comprehensive framework for understanding effects of temperature and offer new insights into the regulation of Notch signaling in stem cell biology.

developmental biology↗

bioRxiv2025

Genetic mutations in GLP-1/Notch pathway reveal distinct mechanisms of Notch signaling in germline stem cell regulation

The Notch signaling pathway is crucial for germline stem cell (GSC) regulation in C. elegans, yet the molecular and biological consequences of GLP-1/Notch mutations remain poorly understood. This study systematically analyzes commonly used and clinically relevant glp-1 loss- and gain-of-function mutations to investigate their effects on Notch activity at chromosomal, cellular, and tissue levels. Using complementary direct readouts of Notch activation, including sygl-1 activation sites, mRNA levels, and germline functional assays of the GSC pool and progenitor zone (PZ), we demonstrate that the severity of glp-1 mutations is dependent on their position within the GLP-1 protein. Our results reveal that NICD mutations reduce Notch transcriptional activation at tissue and cellular levels while having little impact at the chromosomal level, whereas NECD mutations have minimal effects across all biological levels. Furthermore, a series of regression analyses of sygl-1 activation, mRNA production, and PZ size reveal strong correlations, qualifying these readouts as predictive markers for germline function. These findings provide a comprehensive framework for understanding glp-1 mutation effects and offer new insights into the regulation of Notch signaling in stem cell biology.

developmental biology↗

bioRxiv2023

Age-dependent structural and morphological changes of the stem cell niche disrupt spatiotemporal regulation of stem cells and drive tissue disintegration

Aging induces a progressive decline in tissue function, which has been attributed to a decrease in stem cell function. A major factor driving this decline is the aging of the stem cell niche but elucidating molecular mechanisms of the niche aging and its effects on stem cell regulation remain a challenge. Here, we use the Caenorhabditis elegans distal tip cell (DTC), the mesenchymal niche that employs Notch signaling to regulate germline stem cells (GSCs), as an in vivo niche aging model and delineate the molecular details of the DTC/niche aging process and its consequences on GSC function and tissue integrity. Using Notch-dependent transcriptional activation as a direct readout of GSC-DTC/niche interaction and its transcriptional activity as a readout for GSC function, we find that an age-dependent reduction in Notch transcription occurs both at the tissue and the cellular levels, but with its activity at the chromosomal loci remains unaffected. This overall reduction is due to an age-dependent progressive shift in the spatial pattern of Notch-dependent transcription in the germline, resulting in a shift of the GSC pool location and disruption of the tissue integrity. We show that the position of the DTC/niche nucleus determines the location of the Notch-responsive GSC pool, with its correlation to the structure and morphology of the DTC/niche, which also changes during aging. Our findings demonstrate that the stem cell niche undergoes structural and morphological changes during aging and reveal a critical link between these changes and the spatiotemporal regulation of stem cell function.

cell biology↗