Biology subjects

Lecoin, L.

Publications and source records attributed to Lecoin, L..

2 recordsLinked to original sources

bioRxiv2026

Long-projection astrocytes challenge canonical territorial organization in the sleep-promoting VLPO

The ventrolateral preoptic nucleus (VLPO) is a key hypothalamic hub for non-rapid eye movement sleep, yet the glial architecture supporting its circuits remains poorly understood. Here, combining genetic labeling, high-resolution imaging and calcium imaging, we uncover unexpected astrocyte diversity in the VLPO. In addition to classical protoplasmic astrocytes, we identify paired "doublet" astrocytes associated with high local proliferative activity, as revealed by EdU incorporation. We further describe a population of long-projection astrocytes extending processes far beyond canonical astrocytic territories and contacting distant cells. These projections challenge the classical territorial organization of astrocytes and resemble morphologies previously thought to be restricted to hominid brains. Notably, VLPO astrocytes display robust spontaneous Ca{superscript 2} activity and a highly functionally connected network compared to astrocytes in the cortex and hippocampus. Together, these findings reveal specialized astrocyte architectures and enhanced glial network integration within a sleep-promoting nucleus. Reporting summaryBellier et al. identify three astrocyte subtypes in the sleep-promoting VLPO, including long-projection astrocytes with hominid-like morphology. They uncover marked postnatal gliogenesis, distinctive spontaneous Ca{superscript 2} dynamics, and tightly interconnected astrocytic networks, revealing region-specific astrocyte specialization and enhanced glial communication.

neuroscience↗

bioRxiv2025

MAFA Phosphorylation Controls Beta-Cell Identity and Sex-Specific Pancreatic Disease Outcomes

Mafa is a critical transcription factor in pancreatic beta-cell biology, orchestrating insulin expression in response to glucose elevations. As a member of the large MAF protein family, MAFAs stability and activity are intricately regulated by GSK3-mediated phosphorylation. To decipher the functional roles of these phosphorylations, we engineered knock-in mice (Mafa4A/+) in which MAFA is rendered non-phosphorylatable. In all Mafa4A/+ animals, MAFA stability was markedly enhanced. Under high-fat diet (HFD) conditions, Mafa4A/+ males rapidly developed glucose intolerance, which was attributed to impaired glucose-stimulated insulin secretion. Bulk RNA sequencing revealed disrupted beta- cell identity, characterized by increased expression of MODY-associated genes and a delta-cell signature, suggesting beta-to-delta cell reprogramming, a hypothesis supported by lineage- tracing experiments. Conversely, Mafa4A/+ females exhibited hypoglycemia and, with age, developed pronounced inflammatory cystic ducts including mucinous cystic neoplasms (MCNs). Strikingly, MAFA protein was also detected in MCN biopsies from female patients, linking our findings to human pathology. Our results unveil a sex-biased impact of GSK3-mediated MAFA phosphorylation. The male phenotype closely parallels the MODY-like diabetes observed in patients with MAFA S64F mutations, implicating defective phosphorylation in disease etiology. The emergence of MCNs in female mice suggests a novel role for MAFA stability or mutations in the pathogenesis of these enigmatic neoplasms, providing a fresh molecular hypothesis with clinical relevance.

cell biology↗