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Mouse embryonic kidney transplantation identifies maturation defects in the medulla

ABSTRACT: Mouse embryonic kidney transplantation identifies maturation defects in the medulla

PROVIDER: PRJNA1132144 | ENA |

REPOSITORIES: ENA

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Mouse embryonic kidney transplantation identifies maturation defects in the medulla

Project description:Kidney organoids are connected to the host circulation and mature after transplantation. However, they are still immature compared to the adult kidneys, and their precise maturation stages remain unclear. By transplanting the mouse embryonic kidney as a model system for organoid transplantation, we report here the maturation defects of the graft, especially in the medulla. Single cell profiling of the developing kidneys in vivo identified gene sets associated with the maturation of the collecting duct epithelium and medullary stroma. These data revealed an upregulation of genes associated with channel/transporter functions and immune defense, as well as a downregulation of neuronal genes. Using these marker genes, we found that the maturation of the collecting duct and medullary stroma in the grafts barely corresponds to the perinatal stage, which was confirmed histologically by using representative genes. Thus, the gene sets obtained serve as maturation coordinates for the renal medulla and will be helpful in analyzing its maturation defects after transplantation. They will also provide a useful basis for further maturation of transplanted kidney organoids.

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RNA-seq of human kidney cortex and medulla

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RNA-seq of human kidney cortex and medulla

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The effect of cortex/medulla proportions on molecular diagnoses in kidney transplant biopsies: rejection and injury can be assessed in medulla

Project description:Histologic assessment of kidney transplant biopsies relies on cortex rather than medulla, but for microarray studies, the proportion cortex in a biopsy is typically unknown and could affect the molecular readings. The present study aimed to develop a molecular estimate of proportion cortex in biopsies and examine its effect on molecular diagnoses. Microarrays from 26 kidney transplant biopsies divided into cortex and medulla components and processed separately showed that many of the most significant differences were in glomerular genes e.g. NPHS2, NPHS1, CLIC5, PTPRO, PLA2R1, PLCE1, PODXL and REN. Using NPHS2 (podocin) to estimate proportion cortex, we examined whether proportion cortex influenced molecular assessment in the Molecular Microscope Diagnostic System. In 1190 unselected kidney transplant indication biopsies (Clinicaltrials.govNCT01299168), only 11% had <50% cortex. Molecular scores for ABMR, TCMR, and injury were independent of proportion cortex. Rejection was diagnosed in many biopsies that were mostly or all medulla. Agreement in molecular diagnoses in paired cortex/medulla samples (23/26) was similar to biological replicates (32/37). We conclude that NPHS2 expression can estimate proportion cortex; that proportion cortex has little influence on molecular diagnosis of rejection, and that, although histology cannot assess medulla, rejection does occur in medulla as well as cortex.

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Expression data from renal dendritic cells under homeostatic conditions and from donor and host dendritic cells from renal allografts (3 days post-transplantation), isolated from cortex and medulla.

Project description:Renal dendritic cells play key roles in renal homeostasis and during kidney allograft rejection. Microarray analysis aims to evaluate whether dendritic cells modulate their gene expression profile in relation to their distribution in the different renal compartments (with varying biophysical characteristics), under homeostatic conditions and during acute renal allograft rejection (3 days post-transplantation). Renal dendritic cells from homeostatic (healthy) kidneys and donor/host dendritic cells from renal allografts (3 days post-kidney transplantation) were isolated from cortex and medulla, through fluorescence-activated cell sorting (FACS). Total RNA was isolated from FACS-sorted cells and amplified. The cDNA product was fragmented, biotin-labeled and hybridized on Affimetrix arrays.

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Multi-omic Analysis of Primary Human Kidney Tissues Identifies Medulla-Specific Gene Expression Patterns

Project description:The renal medulla is a specialized region of the kidney with important homeostatic functions. It has also been implicated in genetic and developmental disorders and ischemic and drug-induced injuries. Despite its role in kidney function and disease, the medulla’s baseline gene expression and epigenomic signatures have not been well described in the adult human kidney. Here we generate and analyze gene expression (RNA-seq), chromatin accessibility (ATAC-seq), chromatin conformation (Hi-C) and digital spatial profiling data from adult human kidney cortex and medulla. Using data from our carefully annotated specimens, we assign samples in the larger public GTEx database to cortex and medulla, thereby identifying several misassignments and extracting meaningful medullary gene expression signatures. Using integrated analysis of gene expression, chromatin accessibility and conformation profiles, we reveal insights into medulla development and function. Our datasets will also provide a valuable resource for researchers in the GWAS community for functional annotation of genetic variants.

2023-11-15 | GSE235841 | GEO

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