Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

ScRNA-seq of Gene-edited Porcine Kidneys Prior to Xenotransplantation into Cynomolgus Macaques

ABSTRACT: Succesful xenotransplantation of porcine kidneys into humans requires the ubiqutous expression of certain human transgenes. Modern transcriptomics now alllows gene expression to be measured at the per-cell level, which can provide important insights into the expression pattern of these life-sustaining transgenes in a complex organ such as the kidney. Analysis of this scRNA-seq data shows ubiquitous expression of transgenes in most major kidney cell populations which includes various subtypes of endothelial cells.

ORGANISM(S): Sus scrofa

PROVIDER: GSE210557 | GEO | 2023/04/21

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Longitudinal RNA-seq of Gene-edited Porcine Kidneys in Cynomolgus Macaques

Project description:Succesful xenotransplantation of porcine kidneys into humans requires durable expression of certain human transgenes. In order to ensure robust expression through the life of the transplanted kidney, RNA-seq was performed on gene-edited kidneys prior to and during transplantation into cynomolgus macaques. Analysis of this longitudinal transcriptomics data shows robust and stable transgene expression through the lifespan of numerous xenotransplanted organs.

2023-04-21 | GSE210556 | GEO

scRNA-seq of Gene-edited Porcine Kidneys Prior to Xenotransplantation into Cynomolgus Macaques

Project description:scRNA-seq of Gene-edited Porcine Kidneys Prior to Xenotransplantation into Cynomolgus Macaques

| PRJNA866159 | ENA

Spatiotemporal immune atlas of a clinical-grade gene-edited pig-to-human kidney xenotransplant

Project description:Pig-to-human xenotransplantation is rapidly approaching the clinical arena; however, it is unclear which immunomodulatory regimens will effectively control human immune responses to pig xenografts. Here, we transplant a gene-edited pig kidney into a brain-dead human recipient on pharmacologic immunosuppression and study the human immune response to the xenograft using spatial transcriptomics and single-cell RNA sequencing. Human immune cells are uncommon in the porcine kidney cortex early after xenotransplantation and consist of primarily myeloid cells. Both the porcine resident macrophages and human infiltrating macrophages express genes consistent with an alternatively activated, anti-inflammatory phenotype. No significant infiltration of human B or T cells into the porcine kidney xenograft is detectable. Altogether, these findings provide proof of concept that conventional pharmacologic immunosuppression is sufficient to restrict infiltration of human immune cells into the xenograft early after compatible pig-to-human kidney xenotransplantation.

2024-03-27 | GSE242270 | GEO

Clinical and molecular correlation defines activity of physiological pathways in life-sustaining kidney xenotransplantation [scRNA-Seq]

Project description:Progress in clinical translation of gene edited porcine kidney xenotransplantation is accelerating. However, kidney function entails more than removal of metabolic waste products and it is unknown if all endocrine functions will be faithfully reproduced by porcine kidneys in primate recipients. Seventeen cynomolgus macaques with survival >60days after life sustaining kidney xenotransplantation (LSKX) from gene edited Yucatan minipigs underwent measurement of xenograft growth and two kidney dependent endocrine pathways: renin-angiotensin-aldosterone-system (RAAS) and calcium-vitamin D-parathyroid-hormone. Clinical chemistries, plasma-renin-activity, Beta-C-terminal-telopeptide (CTx) assay, RNA-seq, single-cell RNA-seq, and serial ultrasonography were conducted and generalized linear models assessed statistical relationships. Xenografts transplanted from minipigs demonstrated only modest growth (estimated ~8.0% per year) and didn’t significantly contribute to recipient RAAS pathway. However, PTH-independent hypercalcemia and hypophosphatemia were observed and might be xenograft intrinsic suggesting close monitoring and timely intervention during the first month post-transplant. Further study of these phenotypes is warranted in designing prospective clinical trials.

2023-04-25 | GSE216033 | GEO

Clinical and molecular correlation defines activity of physiological pathways in life-sustaining kidney xenotransplantation [RNA-Seq]

2023-04-25 | GSE216029 | GEO

Longitudinal RNA-seq of Gene-edited Porcine Kidneys in Cynomolgus Macaques

Project description:Longitudinal RNA-seq of Gene-edited Porcine Kidneys in Cynomolgus Macaques

| PRJNA866161 | ENA

Life-supporting function of genome edited porcine renal graft in cynomolgus macaques

Project description:This SuperSeries is composed of the SubSeries listed below.

2023-04-25 | GSE211432 | GEO

Carbohydrate antigen microarray analysis of serum IgG and IgM antibodies before and after adult porcine islet xenotransplantation in cynomolgus macaques.

Project description:Understanding the anti-carbohydrate antibody response toward epitopes expressed on porcine cells, tissues, and organs is critical to advancing xenotransplantation toward clinical application. In this study, we determined IgM and IgG antibody specificities and relative concentrations in five cynomolgus monkeys at baseline and at intervals following intraportal xenotransplantation of adult porcine islets. This study utilized a carbohydrate antigen microarray that comprised more than 400 glycoconjugates, including historically reported α-Gal and non-α-Gal carbohydrate antigens with various modifications. The elicited anti-carbohydrate antibody responses were predominantly IgM compared to IgG in 4 out of 5 monkeys. Patterns of elicited antibody responses greater than 1.5 difference (log2 base units; 2.8-fold on a linear scale) from pre-serum to post-serum sampling specific for carbohydrate antigens were heterogeneous and recipient-specific. Increases in the elicited antibody response to α-Gal, Sda, GM2 antigens, or Lexis X antigen were found in individual monkeys. The novel carbohydrate structures Galβ1-4GlcNAcβ1-3Galβ1 and N-linked glycans with Manα1-6(GlcNAcβ1-2Manα1-3)Manβ1-4GlcNAcβ structure were common targets of elicited IgM antibodies. These results provide important insights into the carbohydrate epitopes that elicit antibodies following pig-to-monkey islet xenotransplantation and reveal possible targets for gene editing.

| S-EPMC8211184 | biostudies-literature

Clinical and molecular correlation defines activity of physiological pathways in life-sustaining kidney xenotransplantation

Project description:Clinical and molecular correlation defines activity of physiological pathways in life-sustaining kidney xenotransplantation

| PRJNA891740 | ENA

Gene expression in three tissues from two crab-eating macaques (Macaca fascicularis, cynomolgus monkey).

Project description:We provide RNA-Seq data for cerebral cortex, liver and kidney cortex from two untreated female crab-eating macaques.

2019-05-01 | GSE120935 | GEO