Biology subjects

Jamshidi, N.

Publications and source records attributed to Jamshidi, N..

2 recordsLinked to original sources

bioRxiv2024

Dysfunctional β-cell longevity in diabetes relies on high energy conservation and positive epistasis

Long-lived PFKFB3 expressing {beta}-cells are dysfunctional cells because of prevailing glycolysis that compromises metabolic coupling of insulin secretion. Their accumulation in type-2 diabetes (T2D) appears to be related to the loss of apoptotic competency of cell fitness competition (CFC) that maintains tissue function by favoring constant selection of healthy "winner" cells. To investigate how PFKFB3 can disguise the competitive traits of dysfunctional "loser" {beta}-cells, we analyzed the overlap between human {beta}-cells with bona-fide "loser signature" across diabetes pathologies utilizing the HPAP scRNA-seq and spatial transcriptomics of PFKFB3 positive {beta}-cells from nPOD T2D pancreata. The overlapping transcriptional profile of "loser" {beta}-cells was represented by downregulated ribosomal biogenesis- and genes encoding for mitochondrial respiration. PFKFB3 positive "loser" {beta}-cells had reduced expression of HLA Class I and II genes. Gene-gene interaction analysis revealed that PFKFB3 rs1983890 can interact with anti-apoptotic gene MAIP1 implicating positive epistasis as a mechanism for prolonged survival of "loser" {beta}-cells in T2D. Inhibition of PFKFB3 resulted in the clearance of dysfunctional "loser" {beta}-cells leading to restored glucose tolerance in mouse model of T2D.

cell biology↗

bioRxiv2022

A 3D bioprintable hydrogel with tuneable stiffness for exploring cells encapsulated in matrices of differing stiffnesses

In vitro cell models have undergone a shift from 2D models on glass slides to 3D models that better reflect the native 3D microenvironment. 3D bioprinting promises to progress the field by allowing the high throughput production of reproducible cell-laden structures with high fidelity. As this technology is relatively new, the current stiffness range of printable matrices surrounding the cells that mimics the extracellular matrix environment remains limited. The work presented here aims to expand the range of stiffnesses by utilising a 4-armed polyethylene glycol with maleimide functionalised arms. The complementary crosslinkers comprised a matrix metalloprotease (MMP)-degradable peptide and a 4-armed thiolated polymer which were adjusted in ratio to tune the stiffness. The modularity of this system allows for a simple method of controlling stiffness and the addition of biological motifs. The application of this system in drop-on-demand printing is validated in this work using MCF-7 cells which were monitored for viability and proliferation. This study shows the potential of this system for the high-throughput investigation of the effects of stiffness and biological motif compositions in relation to cell behaviours.

cell biology↗