TFAP2A orchestrates gene regulatory networks and tubular architecture in kidney outer medullary collecting ducts.

Mutations in the transcription factor TFAP2A are linked to congenital anomalies of the kidney and urinary tract in humans. While Tfap2a knockout (KO) in mouse collecting ducts leads to tubular epithelial abnormalities, its precise molecular functions in kidney tubules remain unclear. To investigate Tfap2a-dependent gene regulatory networks in the mouse kidney collecting ducts, we employed conditional knockout (Hoxb7-Cre; Tfap2aflox/flox) models combined with transcriptomics.

[Medical follow-up after solid organs transplantation].

Medical follow-up after the transplantation of solid organs is a key component in ensuring long-term survival of both the graft and the patient. This article outlines the essential principles of post-transplant care for recipients of heart, liver, lung, and kidney transplants. Across all organ types, certain core elements are universally important: monitoring of graft function, individualized adjustment of immunosuppressive therapy, early detection and treatment of rejection episodes, consistent prevention, recognition, and management of infections, professional care for comorbidities, and appropriate cancer screening.

Effect of felzartamab on the molecular phenotype of antibody-mediated rejection in kidney transplant biopsies.

A recent randomized controlled trial demonstrated that treatment with anti-CD38 monoclonal antibody felzartamab suppressed antibody-mediated rejection (ABMR) in kidney transplant patients but with recurrence after treatment in some patients. Here we examined the molecular effects of 6 months of felzartamab treatment on biopsies from the trial using genome-wide microarray analysis, comparing pretreatment, end-of-treatment (week 24) and posttreatment (week 52) biopsies from ten patients treated with felzartamab and ten patients in the placebo group. Felzartamab reduced molecular ABMR activity scores in all nine patients with baseline ABMR activity, selectively suppressing interferon gamma-inducible and natural killer cell transcripts, with minimal effect on ABMR stage-related endothelial transcripts.

A cross-sectional study of the role of epithelial cell injury in kidney transplant outcomes.

Background: Expression of acute kidney injury-associated (AKI-associated) transcripts in kidney transplants may reflect recent injury and accumulation of epithelial cells in "failed repair" states. We hypothesized that the phenomenon of failed repair could be associated with deterioration and failure in kidney transplants.

Methods: We defined injury-induced transcriptome states in 4,502 kidney transplant biopsies injury-induced gene sets and classifiers previously developed in transplants.

Depletion of alloreactive B cells by drug-resistant chimeric alloantigen receptor T cells to prevent transplant rejection.

Antibody-mediated rejection (AMR) remains a major complication after solid organ transplantation (SOT). Current treatment options are inefficient and result in drastic impairment of the general immunity. To selectively eliminate responsible alloreactive B cells characterized by anti-donor-HLA B cell receptors (BCRs), we generated T cells overcoming rejection by antibodies (CORA-Ts) engineered with a novel chimeric receptor comprising a truncated donor-HLA molecule as antigen recognition domain.

Immunosuppression with cyclosporine versus tacrolimus shows distinctive nephrotoxicity profiles within renal compartments.

Aim: Calcineurin inhibitors (CNIs) are the backbone for immunosuppression after solid organ transplantation. Although successful in preventing kidney transplant rejection, their nephrotoxic side effects contribute to allograft injury. Renal parenchymal lesions occur for cyclosporine A (CsA) as well as for the currently favored tacrolimus (Tac).

Epithelial cell states associated with kidney and allograft injury.

The kidney epithelium, with its intricate arrangement of highly specialized cell types, constitutes the functional core of the organ. Loss of kidney epithelium is linked to the loss of functional nephrons and a subsequent decline in kidney function. In kidney transplantation, epithelial injury signatures observed during post-transplantation surveillance are strong predictors of adverse kidney allograft outcomes.

The aging kidney is characterized by tubuloinflammaging, a phenotype associated with MHC-II gene expression.

Introduction: Even during physiologic aging, the kidney experiences a loss of mass and a progressive functional decline. This is clinically relevant as it leads to an increased risk of acute and chronic kidney disease. The kidney tubular system plays an important role in the underlying aging process, but the involved cellular mechanisms remain largely elusive.

The centrosomal protein 83 (CEP83) regulates human pluripotent stem cell differentiation toward the kidney lineage.

During embryonic development, the mesoderm undergoes patterning into diverse lineages including axial, paraxial, and lateral plate mesoderm (LPM). Within the LPM, the so-called intermediate mesoderm (IM) forms kidney and urogenital tract progenitor cells, while the remaining LPM forms cardiovascular, hematopoietic, mesothelial, and additional progenitor cells. The signals that regulate these early lineage decisions are incompletely understood.

Acute kidney injury biomarkers in the single-cell transcriptomic era.

Acute kidney injury (AKI) affects many hospitalized patients and is associated with increased morbidity and mortality even at milder and reversible stages. The current clinical definition relies on serum creatinine increases or decreased urinary output. However, both parameters are of limited use because of poor sensitivity, specificity, and timeliness.

Single-cell transcriptomics reveals common epithelial response patterns in human acute kidney injury.

Background: Acute kidney injury (AKI) occurs frequently in critically ill patients and is associated with adverse outcomes. Cellular mechanisms underlying AKI and kidney cell responses to injury remain incompletely understood.

Methods: We performed single-nuclei transcriptomics, bulk transcriptomics, molecular imaging studies, and conventional histology on kidney tissues from 8 individuals with severe AKI (stage 2 or 3 according to Kidney Disease: Improving Global Outcomes (KDIGO) criteria).

Urinary single-cell sequencing captures kidney injury and repair processes in human acute kidney injury.

Acute kidney injury (AKI) is a major health issue, the outcome of which depends primarily on damage and reparative processes of tubular epithelial cells. Mechanisms underlying AKI remain incompletely understood, specific therapies are lacking and monitoring the course of AKI in clinical routine is confined to measuring urine output and plasma levels of filtration markers. Here we demonstrate feasibility and potential of a novel approach to assess the cellular and molecular dynamics of AKI by establishing a robust urine-to-single cell RNA sequencing (scRNAseq) pipeline for excreted kidney cells via flow cytometry sorting.

Human lungs show limited permissiveness for SARS-CoV-2 due to scarce ACE2 levels but virus-induced expansion of inflammatory macrophages.

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) utilises the angiotensin-converting enzyme 2 (ACE2) transmembrane peptidase as cellular entry receptor. However, whether SARS-CoV-2 in the alveolar compartment is strictly ACE2-dependent and to what extent virus-induced tissue damage and/or direct immune activation determines early pathogenesis is still elusive.

Methods: Spectral microscopy, single-cell/-nucleus RNA sequencing or ACE2 "gain-of-function" experiments were applied to infected human lung explants and adult stem cell derived human lung organoids to correlate ACE2 and related host factors with SARS-CoV-2 tropism, propagation, virulence and immune activation compared to SARS-CoV, influenza and Middle East respiratory syndrome coronavirus (MERS-CoV).

Nuclei Isolation from Adult Mouse Kidney for Single-Nucleus RNA-Sequencing.

The kidneys regulate diverse biological processes such as water, electrolyte, and acid-base homeostasis. Physiological functions of the kidney are executed by multiple cell types arranged in a complex architecture across the corticomedullary axis of the organ. Recent advances in single-cell transcriptomics have accelerated the understanding of cell type-specific gene expression in renal physiology and disease.

What's a Biofilm?-How the Choice of the Biofilm Model Impacts the Protein Inventory of .

The anaerobic pathogen is perfectly equipped to survive and persist inside the mammalian intestine. When facing unfavorable conditions is able to form highly resistant endospores. Likewise, biofilms are currently discussed as form of persistence.

Critical Illness and Systemic Inflammation Are Key Risk Factors of Severe Acute Kidney Injury in Patients With COVID-19.

Introduction: Acute kidney injury (AKI) is an important complication in COVID-19, but its precise etiology has not fully been elucidated. Insights into AKI mechanisms may be provided by analyzing the temporal associations of clinical parameters reflecting disease processes and AKI development.

Methods: We performed an observational cohort study of 223 consecutive COVID-19 patients treated at 3 sites of a tertiary care referral center to describe the evolvement of severe AKI (Kidney Disease: Improving Global Outcomes stage 3) and identify conditions promoting its development.

Kidney Single-cell Transcriptomes Predict Spatial Corticomedullary Gene Expression and Tissue Osmolality Gradients.

Background: Single-cell transcriptomes from dissociated tissues provide insights into cell types and their gene expression and may harbor additional information on spatial position and the local microenvironment. The kidney's cells are embedded into a gradient of increasing tissue osmolality from the cortex to the medulla, which may alter their transcriptomes and provide cues for spatial reconstruction.

Methods: Single-cell or single-nuclei mRNA sequencing of dissociated mouse kidneys and of dissected cortex, outer, and inner medulla, to represent the corticomedullary axis, was performed.

Limited utility of qPCR-based detection of tumor-specific circulating mRNAs in whole blood from clear cell renal cell carcinoma patients.

Background: RNA sequencing data is providing abundant information about the levels of dysregulation of genes in various tumors. These data, as well as data based on older microarray technologies have enabled the identification of many genes which are upregulated in clear cell renal cell carcinoma (ccRCC) compared to matched normal tissue. Here we use RNA sequencing data in order to construct a panel of highly overexpressed genes in ccRCC so as to evaluate their RNA levels in whole blood and determine any diagnostic potential of these levels for renal cell carcinoma patients.

Fluconazole Increases Osmotic Water Transport in Renal Collecting Duct through Effects on Aquaporin-2 Trafficking.

Background: Arginine-vasopressin (AVP) binding to vasopressin V2 receptors promotes redistribution of the water channel aquaporin-2 (AQP2) from intracellular vesicles into the plasma membrane of renal collecting duct principal cells. This pathway fine-tunes renal water reabsorption and urinary concentration, and its perturbation is associated with diabetes insipidus. Previously, we identified the antimycotic drug fluconazole as a potential modulator of AQP2 localization.

Drying and Rainfall Shape the Structure and Functioning of Nitrifying Microbial Communities in Riverbed Sediments.

Non-flow periods in fluvial ecosystems are a global phenomenon. Streambed drying and rewetting by sporadic rainfalls could drive considerable changes in the microbial communities that govern stream nitrogen (N) availability at different temporal and spatial scales. We performed a microcosm-based experiment to investigate how dry period duration (DPD) (0, 3, 6, and 9 weeks) and magnitude of sporadic rewetting by rainfall (0, 4, and 21 mm applied at end of dry period) affected stocks of N in riverbed sediments, ammonia-oxidizing bacteria (AOB) and archaea (AOA) and rates of ammonia oxidation (AO), and emissions of nitrous oxide (NO) to the atmosphere.

Canonical BMP signaling in tubular cells mediates recovery after acute kidney injury.

Bone morphogenetic protein (BMP) signaling has been shown to modulate the development of renal fibrosis in animal models of kidney injury, but the downstream mediators are incompletely understood. In wild-type mice, canonical BMP signaling mediated by SMAD1/5/8 transcription factors was constitutively active in healthy renal tubules, transiently down-regulated after ischemia reperfusion injury (IRI), and reactivated during successful tubular regeneration. We then induced IRI in mice with a tubular-specific BMP receptor 1A (BMPR1A) deletion.

The AP-1-BATF and -BATF3 module is essential for growth, survival and TH17/ILC3 skewing of anaplastic large cell lymphoma.

Transcription factor AP-1 is constitutively activated and IRF4 drives growth and survival in ALK and ALK anaplastic large cell lymphoma (ALCL). Here we demonstrate high-level BATF and BATF3 expression in ALCL. Both BATFs bind classical AP-1 motifs and interact with in ALCL deregulated AP-1 factors.