Biology subjects

Cen, J.

Publications and source records attributed to Cen, J..

3 recordsLinked to original sources

bioRxiv2026

Automated Multimodal Correlative Registration for Organelle-Specific Molecular Imaging

Mapping subcellular drug distribution is essential for understanding trafficking and off-target effects. NanoSIMS enables chemical imaging of labeled therapeutics, but signal interpretation requires ultrastructural correlation with electron microscopy, a manual and laborious process. We present an automated AI-driven pipeline for correlating chemical and ultrastructural images, enabling multiscale, organelle-precise imaging of molecules in cells and tissues. The method integrates bidirectional optical flow, confidence-guided affine transformation, and automated template matching for cross-scale EM alignment. Morphology-rich ion channels (e.g., 32S) estimate transformations that propagate to sparse therapeutic signals (e.g., 79Br, 15N), overcoming low signal-to-noise challenges. We validate this framework across diverse cell and tissue types, tracking oligonucleotide and antibody therapeutics in vitro and in vivo to reveal cell-type- and organelle-specific distribution patterns. This work establishes a generalizable platform for automated multimodal registration and organelle-resolved subcellular pharmacology.

bioinformatics↗

bioRxiv2021

The endoplasmic reticulum-plasma membrane tethering protein TMEM24 is a regulator of cellular Ca2+ homeostasis

Endoplasmic reticulum (ER) - plasma membrane (PM) contacts are sites of lipid exchange and Ca2+ transport, and both lipid transport proteins and Ca2+ channels specifically accumulate at these locations. In pancreatic {beta}-cells, both lipid- and Ca2+ signaling are essential for insulin secretion. The recently characterized lipid transfer protein TMEM24 dynamically localize to ER-PM contact sites and provide phosphatidylinositol, a precursor of PI(4)P and PI(4,5)P2, to the plasma membrane. {beta}-cells lacking TMEM24 exhibit markedly suppressed glucose-induced Ca2+ oscillations and insulin secretion but the underlying mechanism is not known. We now show that TMEM24 only weakly interact with the PM, and dissociates in response to both diacylglycerol and nanomolar elevations of cytosolic Ca2+. Release of TMEM24 into the bulk ER membrane also enables direct interactions with mitochondria, and we report that loss of TMEM24 results in excessive accumulation of Ca2+ in both the ER and mitochondria and in impaired mitochondria function.

cell biology↗

bioRxiv2020

Angiotensin II induces apoptosis in human induced pluripotent stem cell-derived cardiomyocytes

BackgroundThe renin-angiotensin system (RAS) functions fundamentally to regulate the pathological process of cardiovascular diseases, such as heart failure and hypertension. As the major effector in RAS, angiotensin II activates angiotensin II receptors to initiate the downstream pathways, which lead to the phenotypes including apoptosis, hypertrophy, and cardiac remodeling. Human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CM) are being applied as a promising platform for personalized medicine to heart diseases. However, whether angiotensin II induces apoptosis in iPSC-CM is still obscure, which raises an uncertainty about the clinical applications of iPSC-CM. MethodsWe treated iPSC-CM with angiotensin II at eight concentrations (0 nM, 1 nM, 10 nM, 100 nM, 1 M, 10 M, 100 M and 1 mM) and four incubation durations (24 hours, 48 hours, 6 days and 10 days), then PrestoBlue reagent and a apoptosis marker were used to examine the viability and apoptosis status of cardiomyocytes from each group. The expression levels of some apoptosis and proliferation related genes were also analyzed. ResultsHigh concentration angiotensin II with a long-term treatment caused apoptosis and cell viability drop-off in iPSC-CM. Specifically, under a 10-day treatment with 1 mM angiotensin II, the viability of iPSC-CM was reduced by an average of 41% (p=2.073E-08), and the percentage of apoptotic cells was 2.74 times higher than the controls averagely (p=6.248E-12). The data mining of previous RNA-seq data revealed that angiotensin II receptor type I was the major receptor in iPSC-CM. Conclusions: For the first time, our data confirmed the apoptotic effect of angiotensin II to iPSC-CM. The angiotensin II concentrations and exposure time for apoptosis induction were depicted in our study, which provided supports to iPSC-CM as an in vitro model for cardiovascular disease study.

cell biology↗