Biology subjects

Krispin, S.

Publications and source records attributed to Krispin, S..

3 recordsLinked to original sources

bioRxiv2024

Organellomics: AI-driven deep organellar phenotyping of human neurons

Systematic assessment of organelle architectures, termed the organellome, offers valuable insights into cellular states and pathomechanisms, but remains largely uncharted. Here, we present a deep phenotypic learning based on vision transformers, resulting in the Neuronal Organellomics Vision Atlas (NOVA) model that studies confocal images of more than 30 markers of distinct membrane-bound and membraneless organelles in 11.5 million images of human neurons. Organellomics analysis quantifies perturbation-induced changes in organelle localization and morphology using a rigorous mixed-effects meta-analytic framework that accounts for sampling variance and experimental heterogeneity. Applying this approach, we delineate phenotypic alterations in neurons carrying ALS-associated mutations and uncover a physical and functional crosstalk between cytoplasmic mislocalized TDP-43, a hallmark of ALS, and processing bodies (P-bodies), membraneless organelles regulating mRNA stability. These findings are validated in patient-derived neurons and human neuropathology. NOVA establishes a scalable framework for quantitative mapping of subcellular phenotypes and provides a new avenue for investigating the neurocellular basis of disease.

systems biology↗

bioRxiv2021

Oxytocin Signaling Regulates the Homeostatic Response to Cold Stress in Poikilothermic Vertebrates

When exposed to low temperature, homeothermic vertebrates maintain internal body temperature by activating thermogenesis and by altered metabolism, synchronized by neuroendocrine responses. Although such physiological responses also occur in poikilothermic vertebrates, the prevailing notion is that their reactions are passive. Here, we explored molecular hypothalamic and physiological responses to cold stress in the tropical poikilotherm Nile tilapia (Oreochromis niloticus). We show that cold exposed tilapia exhibit complex homeostatic responses, including increased hypothalamic oxytocin, plasma glucose and cortisol concomitant with reduced plasma lactate and metabolic rate. Pharmacological or genetic blockage of oxytocin signaling further affected metabolic rate in two cold-exposed poikilothermic models. This indicates that oxytocin, a known thermoregulator in homeotherms, actively regulates temperature-related homeostasis in poikilotherms. Overall, our findings show that the brain of poikilotherms actively responds to cold temperature by regulating metabolic physiology. Moreover, we identify oxytocin signaling as an adaptive and evolutionarily conserved metabolic regulator of temperature-related homeostasis.

physiology↗

bioRxiv2021

Anatomy and Development of the Pectoral Fin Vascular Network in the Zebrafish

The pectoral fins of teleost fish are analogous structures to human forelimbs, and the developmental mechanisms directing their initial growth and patterning are conserved between fish and tetrapods. The forelimb vasculature is critical for limb function, and it appears to play important roles during development by promoting development of other limb structures, but the steps leading to its formation are poorly understood. In this study, we use high-resolution imaging to document the stepwise assembly of the zebrafish pectoral fin vasculature. We show that fin vascular network formation is a stereotyped, choreographed process that begins with the growth of an initial vascular loop around the pectoral fin. This loop connects to the dorsal aorta to initiate pectoral vascular circulation. Pectoral fin vascular development continues with concurrent formation of three elaborate vascular plexuses, one in the distal fin that develops into the fin ray vasculature and two near the base of the fin in association with the developing fin musculature. Our findings detail a complex yet highly choreographed series of steps involved in the development of a complete, functional organ-specific vascular network. SUMMARY STATEMENTThe stereotyped assembly of the pectoral fin vasculature is documented from first migratory sprout into the limb bud, to the adult-like form of the four week old larva.

developmental biology↗