Biology subjects

Burg, A.

Publications and source records attributed to Burg, A..

4 recordsLinked to original sources

bioRxiv2025

Co-Stimulatory Blockade Prevents Intragraft Accrual of Class-Switched, Activated B Cells Despite Failing to Prevent T-Cell Mediated Rejection

Previously, we defined the transcriptomes and clonality of intragraft CD8+ T cell during renal allograft rejection. Here, using single cell RNA sequencing (scRNAseq), we investigated non-CD8+ immune cells during T-cell-mediated rejection (TCMR) under different maintenance immunosuppression (mIS) regimens: tacrolimus, and co-stimulatory blockade (CoB) with belatacept (CTLA4-Ig) or iscalimab (anti-CD40). Myeloid cells comprised of DCs, monocytes and macrophages whose proportion and gene expression were similar between mIS regimens. Given their transcriptiomic similarities, we analyzed publicly-available scRNAseq/CITEseq datasets as well as immunofluorescence staining to resolve independent subpopulations of {gamma}/{delta} T cells and NK cells. Intragraft B cells consisted of clusters of naive, plasmablast, and class-switched B (BCS) cells, with the latter being diminished in CoB mIS. Intragraft CD4+ T cells consisted of FoxP3+ regulatory (Treg), exhausted, Th17, and CXCL13+ peripheral helper (Tph) cells whose proportions differed based in mIS, and the latter two had increased clonal expansion. Notably, cell-cell communication analysis indicated Th17 and Tph cell interactions with BCS cells in tacrolimus, but not CoB, samples. Thus, although failing to prevent TCMR, CoB mIS modulates the accrual of CD4+ T cells and inhibits the intragraft accrual of BCS cells, possibly reflective of clinical observations of less chronic antibody-mediated rejection under CoB mIS.

immunology↗

bioRxiv2024

Gucy1α1 specifically marks kidney, heart, lung and liver fibroblasts

Fibrosis is a common outcome of numerous pathologies, including chronic kidney disease (CKD), a progressive renal function deterioration. Current approaches to target activated fibroblasts, key effector contributors to fibrotic tissue remodeling, lack specificity. Here, we report Gucy11 as a specific kidney fibroblast marker. Gucy11 levels significantly increased over the course of two clinically relevant murine CKD models and directly correlated with established fibrosis markers. Immunofluorescent (IF) imaging showed that Gucy11 comprehensively labelled cortical and medullary quiescent and activated fibroblasts in the control kidney and throughout injury progression, respectively. Unlike traditionally used markers platelet derived growth factor receptor beta (Pdgfr{beta}) and vimentin (Vim), Gucy11 did not overlap with off-target populations such as podocytes. Notably, Gucy11 labelled kidney fibroblasts in both male and female mice. Furthermore, we observed elevated GUCY11 expression in the human fibrotic kidney and lung. Studies in the murine models of cardiac and liver fibrosis revealed Gucy11 elevation in activated Pdgfr{beta}-, Vim- and alpha smooth muscle actin (Sma)-expressing fibroblasts paralleling injury progression and resolution. Overall, we demonstrate Gucy11 as an exclusive fibroblast marker in both sexes. Due to its multiorgan translational potential, GUCY11 might provide a novel promising strategy to specifically target and mechanistically examine fibroblasts.

molecular biology↗

bioRxiv2021

A neural progenitor mitotic wave is required for asynchronous axon outgrowth and morphology

Spatiotemporal mechanisms generating neural diversity are fundamental for understanding neural processes. Here, we investigated how neural diversity arises from neurons coming from identical progenitors. In the dorsal thorax of Drosophila, rows of mechanosensory organs originate from the division of sensory organ progenitor (SOPs). We show that in each row of the notum, a central SOP divides first, then neighboring SOPs divide, and so on. This centrifugal wave of mitoses depends on cell-cell inhibitory interactions mediated by SOP cytoplasmic protrusions and Scabrous, a secreted protein interacting with the Delta/Notch complex. Furthermore, when the mitotic wave was abolished, axonal growth was more synchronous, axonal terminals had a complex branching pattern and fly behavior was impaired. We show that the temporal order of progenitor divisions influences the birth order of sensory neurons, axon branching and impact on grooming behavior. These data support the idea that developmental timing controls axon wiring neural diversity.

developmental biology↗

bioRxiv2018

The BTB-ZF transcription factor Tramtrack 69 shapes neural cell lineages by coordinating cell proliferation and cell fate

Cell diversity in multicellular organisms relies on coordination between cell proliferation and the acquisition of cell identity. The equilibrium between these two processes is essential to assure the correct number of determined cells at a given time at a given place. Here, we show that Tramtrack-69 (Ttk69, a BTB-ZF transcription factor ortholog of the human PLZF factor) plays an essential role in controlling this balance. In the Drosophila bristle cell lineage, producing the external sensory organs composed by a neuron and accessory cells, we show that ttk69 loss of function leads to supplementary neural-type cells at the expense of accessory cells. Our data indicate that Ttk69 (1) promotes cell-cycle exit of newborn terminal cells by downregulating cycE, the principal cyclin involved in S-phase entry and (2) regulates cell fate acquisition and terminal differentiation by downregulating the expression of hamlet and upregulating that of Suppressor of Hairless, two transcription factors involved in neural-fate acquisition and accessory-cell differentiation, respectively. Thus, Ttk69 plays a central role in shaping neural cell lineages by integrating molecular mechanisms that regulate progenitor cell-cycle exit and cell-fate commitment.\n\nSummary statementTramtrack-69, a transcription factor orthologous to the human tumor-suppressor PLZF, plays a central role in precursor cell lineages by integrating molecular mechanisms that regulate progenitor cell-cycle exit and cell-fate determination.

developmental biology↗