Biology subjects

Mitchell, B. M.

Publications and source records attributed to Mitchell, B. M..

3 recordsLinked to original sources

bioRxiv2026

The Effects of Hypertension on Signaling Dynamics in Rare Renal Cell Types

Hypertension (HTN) is the most prevalent risk factor for severe cardiovascular disease and can cause major renal damage, inflammation, and immune cell accumulation. Lymphatic endothelial cells (LECs) are involved in the removal of pro-inflammatory immune cells and cytokines and kidney-specific augmentation of lymphangiogenesis can prevent or reduce HTN. In our previous paper, we performed single-cell RNA sequencing (scRNAseq) on CD31+/podoplanin+ renal cells from mice that underwent angiotensin II-induced (A2HTN) or salt sensitive (SSHTN) models of HTN (and their respective controls) and identified populations of LECs, myeloid immune cells (MICs), and a novel multipotent population we dubbed support cells (SCs). Using NicheNet, we compared baseline signaling between these three cell types in control samples and differences in signaling between control and HTN samples in both LECs and SCs. Ligands with high regulatory potential were identified for all three cell types, with Tgfb1 having the strongest and most consistent activity across all cell types. When comparing control and HTN samples in both LECs and SCs, HTN samples consistently had a larger number of downstream targets enriched and targets that were enriched in HTN samples also corresponded to significantly increased differentially expressed genes (p<0.01) as reported previously. Significant GO terms (p<0.01) were identified from targets and showed a shift in HTN samples away from homeostatic processes and toward growth and proliferation in LECs and translation and metabolism in SCs. Validation and manipulation of the ligand-receptor-target links identified here may provide novel approaches to reduce renal inflammation and immune cell activation. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=76 SRC="FIGDIR/small/701352v1_ufig1.gif" ALT="Figure 1"> View larger version (18K): org.highwire.dtl.DTLVardef@88cdb9org.highwire.dtl.DTLVardef@17a4ecforg.highwire.dtl.DTLVardef@cc0a3borg.highwire.dtl.DTLVardef@1b3c18a_HPS_FORMAT_FIGEXP M_FIG C_FIG Created with BioRender.com

pathology↗

bioRxiv2026

Nephron-associated Support Cell Transcriptional Plasticity Expands in Hypertension

Hypertension (HTN) affects over one billion people worldwide and can lead to debilitating cardiovascular and renal conditions if left untreated. Cell death in the kidneys and the inflammation that follows are among the primary effects of chronically elevated blood pressure. There are several cell types throughout the body with immunomodulatory, anti-inflammatory, and pro-regenerative properties that support tissue homeostasis and recent studies have highlighted their therapeutic potential in HTN and kidney-related conditions. In our previous paper, we found a pool of multipotent nephron-associated support cells (SCs) in single-cell RNA sequencing samples of CD31+ and podoplanin+ cells taken from the kidneys of hypertensive mice generated through two mouse models of HTN. Despite remaining roughly constant in number between HTN and control groups, these SCs had 299 differentially expressed genes (p<0.01), 51 and 86 enriched pathways (p<0.01) in the M2 and M5 Molecular Signatures Database gene sets, respectively, and 180 HTN-specific regulons. We also compared lymphatic endothelial cells (LECs) and SCs from HTN and control groups and identified 3636 differentially expressed genes (p<0.01), 537 M2 and 415 M5 enriched pathways (p<0.01), and 218 LEC-specific and 227 SC-specific regulons in the HTN samples. SCs from mice with HTN were more resistant to inflammation-induced changes compared to LECs, and had downregulated stem cell suppressive genes and upregulated genes related to stem cell proliferation and regeneration. Graphical AbstractCreated with BioRender.com O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=71 SRC="FIGDIR/small/699969v1_ufig1.gif" ALT="Figure 1"> View larger version (21K): org.highwire.dtl.DTLVardef@f48eecorg.highwire.dtl.DTLVardef@1d32b85org.highwire.dtl.DTLVardef@ce3a1corg.highwire.dtl.DTLVardef@1491c45_HPS_FORMAT_FIGEXP M_FIG C_FIG

pathology↗

bioRxiv2023

Single-cell RNA sequencing identifies response of renal lymphatic endothelial cells to acute kidney injury

The inflammatory response to acute kidney injury (AKI) likely dictates future renal health. Lymphatic vessels are responsible for maintaining tissue homeostasis through transport and immunomodulatory roles. Due to the relative sparsity of lymphatic endothelial cells (LECs) in the kidney, past sequencing efforts have not characterized these cells and their response to AKI. Here we characterized murine renal LEC subpopulations by single-cell RNA sequencing and investigated their changes in cisplatin AKI. We validated our findings by qPCR in LECs isolated from both cisplatin-injured and ischemia reperfusion injury, by immunofluorescence, and confirmation in in vitro human LECs. We have identified renal LECs and their lymphatic vascular roles that have yet to be characterized in previous studies. We report unique gene changes mapped across control and cisplatin injured conditions. Following AKI, renal LECs alter genes involved endothelial cell apoptosis and vasculogenic processes as well as immunoregulatory signaling and metabolism. Differences between injury models are also identified with renal LECs further demonstrating changed gene expression between cisplatin and ischemia reperfusion injury models, indicating the renal LEC response is both specific to where they lie in the lymphatic vasculature and the renal injury type. How LECs respond to AKI may therefore be key in regulating future kidney disease progression.

pathology↗