Biology subjects

Sultana, Z.

Publications and source records attributed to Sultana, Z..

4 recordsLinked to original sources

bioRxiv2025

Spatial Analysis of T Cell Clonality in Autoimmune Kidney Disease Using TRV Probes

Hypothesizing that the localization of T cell clones correlates with immune function, our goal was to develop an unbiased method to study the spatial distribution of T cells in tissues. We created an in situ hybridization panel with 248 probes that identify immune and tissue cell types, and 132 probes for all variable TRAV, TRBV, TRGV, and TRDV gene segments. Applying this approach to analyze renal biopsies from patients with autoimmune kidney disease, combinations of TRV segments provided spatial information about T cell clonality. Confined clusters of clonally related {beta} T cells were found in proximity to increased numbers of antigen-presenting cells, B cells, and other T cells, reflecting local immune cell interactions. {gamma}{delta} T cells were more frequently located outside or at their periphery of T cell infiltration areas. In conclusion, integrating spatial information with TCR clonotype analysis provided new insights into the organization of immune responses at the tissue level.

immunology↗

bioRxiv2025

Coupling of habitat-preference barriers leads to reproductive isolation in sympatric speciation

Habitat preference is a widely recognized mechanism of reproductive isolation, yet its role in initiating premating barriers and coupling with other barrier mechanisms to establish robust and irreversible reproductive isolation (RI) in sympatric speciation remains unclear. In this study, we developed mathematical models and computer applications to investigate one- and two-allele models of habitat-preference barriers in sympatric populations under disruptive ecological selection. We examined two spatial arrangements: an open-space model inspired by sympatric cichlid fishes that meet in open water with niche habitats that are small relative to lake size, and a no-open-space model inspired by sympatric hawthorn and apple maggot flies that move directly between trees without lingering in midair. Next, we examined coupling between habitat-preference barriers and a two-allele mating-bias barrier developed in a prior study to analyze how their invasion and coupling dynamics could lead to stronger RI. Our findings confirm that habitat preference is an independent mechanism capable of establishing initial premating barriers in sympatric speciation. Moreover, it can couple with additional barriers, such as those based on mating-trait discrimination, to enhance overall RI. Because habitat preference is an adaptive barrier mechanism, its invasion and coupling are driven by selection pressures arising from maladaptive hybrid loss, and it is readily reversed when disruptive ecological selection weakens. The one-allele model is easier to evolve than the two-allele model because it is immune to recombination by gene flow. Habitat-preference barriers can facilitate the emergence of mating-bias barriers. Open-space systems provide fewer opportunities for inter-niche encounters and tend to result in stronger RI compared to no-open-space systems. By elucidating the habitat-preference mechanism, our study reinforces the important role of habitat-preference barriers in sympatric speciation. It also provides insights into a wide range of premating isolating mechanisms--temporal, behavioral, and mechanical--that function similarly by reducing mating encounters.

evolutionary biology↗

bioRxiv2025

Computer Simulations and Analyses of Coupling Among Reproductive Barriers in Late-Stage Sympatric Speciation

The mechanisms driving sympatric speciation remain an unresolved challenge in evolutionary biology. In nature, closely related "good" species are observed to possess multiple different barriers in their genomes that collectively generate strong and irreversible reproductive isolation (RI). Theorists hypothesize that early-stage mechanisms responsible for establishing an initial reproductive barrier differ from those driving the coupling of barriers in later stages of sympatric speciation. In a prior study, we developed a two-allele mathematical model of mating-bias traits to demonstrate how initial premating RI can arise in a sympatric population under disruptive ecological selection. Here, we extend this model to investigate how different pre- and post-mating barriers can couple with such an initial barrier and with one another during late-stage sympatric speciation to establish strong and irreversible RI. We developed computer applications to examine the properties of various barrier mechanisms and the conditions required for their invasion and coupling. Early-stage, adaptive premating barriers, driven by maladaptive hybrid loss, are effective in establishing initial RI and coupling with other barriers but are easily reversed if disruptive ecological selection weakens. Late-stage barriers, by contrast, often rely on earlier barriers to create an environment of reduced gene flow to facilitate their invasion and coupling. Mutations reducing hybrid viability are underdominant in inter-niche matings and can only invade by hitchhiking with barriers conferring a fitness advantage. Chromosomal inversions, an adaptive late-stage mechanism, can combine different barrier properties into a supergene and gain a net fitness advantage to invade and couple with other barriers to create strong and less reversible RI. Late-stage nonadaptive Bateson-Dobzhansky-Muller (BDM) barriers evolve more slowly but confer the strongest and least reversible RI. Our findings reveal a positive feedback loop in which early-stage barriers facilitate the establishment of late-stage barriers, while late-stage barriers strengthen and secure early-stage barriers. This positive reinforcement progressively strengthens overall RI until it becomes irreversible. By examining the properties and invasion dynamics of various barrier mechanisms, this study complements our previous study to propose a comprehensive process of sympatric speciation that explains how barriers emerge and couple to complete the speciation process.

evolutionary biology↗

bioRxiv2024

Spatio-temporal interaction of immune and renal cells determines glomerular crescent formation in autoimmune kidney disease

Rapidly progressive glomerulonephritis (RPGN) is the most aggressive group of autoimmune kidney disease with the worst prognosis. Anti-neutrophil cytoplasmic antibody (ANCA) associated vasculitis, anti-glomerular basement membrane (anti-GBM) and lupus nephritis are the most common causes of RPGN and are characterized by the formation of glomerular crescents and infiltration of leukocytes that eventually lead to glomerulosclerosis and kidney failure. In this work, we used high-resolution spatial transcriptomics of 32 ANCA, 19 lupus nephritis, 6 anti-GBM, and 6 control patients to understand how intercellular signaling between immune and renal tissue cells leads to renal inflammation and glomerular injury. Using 3,218,210 immune and kidney cells, we observed that the biological pathways involved in the sequence of glomerular crescent formation are similar across the diseases. While innate immune cells infiltrated the glomerular compartment relatively early, later increases in adaptive immune cells were largely restricted to the periglomerular regions. These changes in immune cells temporally correlated with increases in glomerular parietal epithelial (PEC) and fibrotic mesangial cells, suggesting disease-relevant functional signaling between these immune and renal cells. Cell communication analysis revealed early disease PDGF signaling from epithelial and mesangial cells to PECs, causing their activation and proliferation. At later stages, TGF-{beta} signaling from macrophages, T cells, epithelial cells, and mesangial cells to PECs triggered the expression of extracellular matrix components resulting in glomerulosclerosis. Our results highlight a spatio-temporally conserved progression into glomerular crescents and sclerosis for ANCA, lupus nephritis, and anti-GBM disease, which is driven by consecutive PDGF and TGF-{beta} signaling to PECs.

immunology↗