Biology subjects

Sabbineni, B.

Publications and source records attributed to Sabbineni, B..

3 recordsLinked to original sources

bioRxiv2026

Functional, transcriptomic, and proteomic profiles of human primary and stem cell-derived beta cells in a state of high insulin production and increased fragility

Insulin production is a cardinal feature of pancreatic {beta} cells. Studies in rodents show that {beta} cells can switch between low and high insulin gene activity states and that elevated insulin production makes {beta} cells more vulnerable to stresses associated with diabetes. In people, genetically elevated insulin production increases the risk of type 1 diabetes. Via effects on obesity, hyperinsulinemia contributes to the pathogenesis of type 2 diabetes. Here, we characterize {beta} cells in low and high INS gene activity states sorted from primary human islets transduced with INS-GFP adenovirus and differentiated INS-EGFP knock-in embryonic stem cells (SC{beta} cells). We profile {beta} cell function, protein synthesis, resilience to diabetes associated stress, single {beta} cell transcriptomes and their co-activity networks, and purified {beta} cell proteomes. We show that human {beta} cells transition between distinct states. High INS cells have elevated maturity marker mRNAs and proteins, increased protein translation, are larger, but also more susceptible to cell death when exposed to diabetes-relevant stresses. We also catalogue thousands of differences in proteins in high INS stem cell-derived {beta} cells compared directly with high INS primary {beta} cells. Our study improves our understanding of the delicate balance between insulin production and {beta} cell resilience and guides the engineering of better {beta} cells. Blurbtranscriptional, proteomic, and functional analyses of insulin gene expression states in human {beta} cells from donor islets and stem cells Key findingsO_LIWe identify high and low INS gene activity states in human insulin-producing cells from donor islets and embryonic stem cell differentiations. C_LIO_LIWe characterize the relationship between insulin production and fragility, demonstrating that increased insulin production comes at a cost of reduced resilience to multiple stresses. C_LIO_LIFunctional, transcriptomic, and proteomic analyses identify similarities and differences between how primary and stem cell-derived {beta} cells manage stress and insulin production. C_LIO_LIWe report a comprehensive side-by-side proteomic analysis of purified primary and stem cell- derived {beta} cells in the high INS state and identify differences in protein production and secretion machinery, providing a roadmap for making better {beta} cells. C_LI

physiology↗

bioRxiv2025

Predicting and Controlling Collective Fate in Multicellular Systems

Collective behavior is a defining property of multicellular systems, where coordinated outcomes emerge from local cell-cell interactions. Yet the quantitative rules linking single-cell decision-making to tissue-scale organization remain poorly resolved. Here, we develop a quantitative framework that defines an order parameter predicting when initially disordered colonies undergo a transition to ordered fate alignment and when minimal, localized inputs can redirect their collective state. This analysis reveals a distinct control regime in which multicellular assemblies become susceptible to a single engineered "guide" cell. We validate these predictions by introducing guide cells that integrate into unperturbed colonies and redirect fate patterns within the theoretically defined control windows. Together, these results connect single-cell decision rules to emergent tissue-level organization and establish a generalizable biological control strategy in which a minority engineered subset can reliably redirect the developmental trajectory of a much larger multicellular population. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=65 SRC="FIGDIR/small/693804v1_ufig1.gif" ALT="Figure 1"> View larger version (24K): org.highwire.dtl.DTLVardef@37baeforg.highwire.dtl.DTLVardef@d1d86aorg.highwire.dtl.DTLVardef@d7375eorg.highwire.dtl.DTLVardef@1741e9a_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOSummary figure:C_FLOATNO Emergence, Scaling, and Control of Multicellular Collective Order. (A) Cell-number-dependent collective order. Sparse colonies lack coordination and yield disordered fate distributions; dense colonies exhibit coordinated, ordered outcomes. (B) Collective order rises with colony compactness ({propto} cell density) and collapses across colony radii R onto a single curve. (C) Once coordination emerges, a single "guide cell" can steer fate-analogous to a sheepdog guiding a flock. The herding efficacy exhibits a biphasic window versus cell number. C_FIG

systems biology↗

bioRxiv2024

Signal transduction pathways controlling Ins2 gene activity and β cell state transitions

Pancreatic {beta} cells exist in low and high insulin gene activity states that are dynamic on a scale of hours to days. Here, we used live 3D imaging, mass spectrometry proteomics, and targeted perturbations of {beta} cell signaling to comprehensively investigate Ins2(GFP)HIGH and Ins2(GFP)LOW {beta} cell states. We identified the two Ins2 gene activity states in intact isolated islets and showed that cells in the same state were more likely to be nearer to each other. We report the proteomes of pure {beta} cells to a depth of 5555 proteins and show that {beta} cells with high Ins2 gene activity had reduced {beta} cell immaturity factors, as well as increased translation. We identified activators of cAMP signaling (GLP1, IBMX) as powerful drivers of transitions from Ins2(GFP)LOW to the Ins2(GFP)HIGH states. Okadaic acid and cyclosporine A had the opposite effects. This study provides new insight into the proteomic profiles and regulation of {beta} cell states.

cell biology↗