Biology subjects

Vasu, S.

Publications and source records attributed to Vasu, S..

2 recordsLinked to original sources

bioRxiv2025

Identification and Characterization of Adult Islet Pancridia Cells Capable of Differentiating into Islet Organoids

Multipotent progenitor-like cells have been identified in the adult pancreas under various physiological and pathological conditions. Here, we identify and characterize a subset of adult pancreas-derived cells, termed islet pancridia cells (IPCs), that can be expanded in vitro and retain the potential for endocrine differentiation and islet cell function. Single-cell RNA sequencing of expanded pancridia revealed transcriptomic profiles resembling immature beta cells, enriched with markers of epithelial-mesenchymal transition. A CD9, PROCR subpopulation of IPCs formed IPC clusters marked by restricted expression of RGS16, a known islet progenitor marker. In vivo, co-transplantation of expanded IPCs with a subtherapeutic dose of islets significantly improved graft function and partially restored native pancreatic endocrine activity in streptozotocin-induced diabetic mice. In vitro, treatment of RGS16 IPC clusters with the small molecule ISX9 induced differentiation into islet organoids that co-expressed and secreted insulin and glucagon. ISX9-mediated differentiation was driven by calcineurin/NFAT-dependent recruitment of the histone acetyltransferase p300 and displacement of histone deacetylases (HDACs) at the RFX6 and NEUROD1 promoters. Pre-treatment with the HDAC inhibitor ITF2357 further enhanced islet cell differentiation by promoting chromatin remodeling and facilitating NFAT-targeted recruitment of p300. These findings uncover calcium-dependent and epigenetic mechanisms that regulate the differentiation of multipotent CD9, PROCR, RGS16 IPCs into functional islet organoids and offer potential strategies for regenerating islet cell mass to treat diabetes.

developmental biology↗

bioRxiv2019

Activity/rest rhythms of Drosophila populations selected for divergent eclosion timing under temperature cues

Despite the fact that the rhythm in adult emergence and rhythm in locomotor activity are two different rhythmic phenomena that occur at distinct life-stages of the fly life cycle, previous studies have hinted at similarities in certain aspects of the organisation of the circadian clock driving these two rhythms. In an earlier study, we have shown that selection on timing of adult emergence behaviour in populations of Drosophila melanogaster leads to the co-evolution of temperature sensitivity of circadian clocks driving eclosion. In this study, we were interested in asking if temperature sensitivity of the locomotor activity rhythm has evolved in our populations with divergent timing of adult emergence rhythm, with the goal of understanding the extent of similarity (or lack of it) in circadian organisation between the two rhythms. We found that in response to simulated jetlag with temperature cycles, late chronotypes (populations selected for predominant emergence during dusk) indeed re-entrain faster than early chronotypes (populations selected for predominant emergence during dawn), thereby indicating enhanced sensitivity of the activity/rest clock to temperature cues in these stocks (entrainment is the synchronisation of internal rhythms to cyclic environmental time-cues). Additionally, we found that late chronotypes show higher plasticity of phases across regimes, day-to-day stability in phases and amplitude of entrainment, all indicative of enhanced temperature sensitive activity/rest rhythms. Our results highlight remarkably similar organisation principles between emergence and activity/rest rhythms.

animal behavior and cognition↗