Cellular dynamics of pig-to-human kdiney xenotransplantation [single cell RNA-seq]
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PROVIDER: PRJNA1080196 | ENA |
REPOSITORIES: ENA
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Project description:Cellular dynamics of pig-to-human kdiney xenotransplantation [RNA-seq]
| PRJNA1080197 | ENA
Project description:We performed comprehensive single-cell RNA sequencing (scRNA-seq) analyses of the two porcine xenografts and their contralateral untransplanted kidneys to dissect xenotransplantation-associated cellular dynamics and xenograft-recipient interactions. We additionally performed longitudinal bulk RNA-seq on core biopsies to dissect the time-resolved physiological changes of the xenografts and longitudinal scRNA-seq of peripheral blood mononuclear cells (PBMCs) to detect recipient’s immune responses across time.
2024-06-30 | GSE257542 | GEO
Project description:We performed comprehensive single-cell RNA sequencing (scRNA-seq) analyses of the two porcine xenografts and their contralateral untransplanted kidneys to dissect xenotransplantation-associated cellular dynamics and xenograft-recipient interactions. We additionally performed longitudinal bulk RNA-seq on core biopsies to dissect the time-resolved physiological changes of the xenografts and longitudinal scRNA-seq of peripheral blood mononuclear cells (PBMCs) to detect recipient’s immune responses across time.
2024-06-30 | GSE257541 | GEO
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
Project description:Although pig-to-nonhuman primate (NHP) corneal xenotransplantation has shown long-term graft survival, xenogeneic antigenrelated immune responses are still stronger than allogenic antigen-associated responses. Therefore, there is an unmet need to investigate major rejection pathways in corneal xenotransplantation, even with immunosuppression. This study aimed to identify biomarkers in aqueous humor for predicting rejection and to investigate rejection-related pathways in grafts from NHPs transplanted with porcine corneas following administration of steroids combined with tacrolimus/rituximab. NHPs who had received corneas from wild‐type (WT) or α‐1,3‐galactosyltransferase gene‐knockout (GTKO) pigs were divided into groups with or without rejection according to clinical examinations. Liquid chromatography-mass spectrometry (LC-MS) was used to analyze the proteomes of corneal tissues or aqueous humor. The biological functions of differentially expressed proteins (DEPs) were assessed using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) for pathways and protein–protein interaction network analysis. Among the 66 DEPs in aqueous humor, complement proteins (C3, C5, and C9) and cholesterol metabolic proteins (APOA1 and APOA2) were related to xenogeneic rejection as biomarkers, and alternative pathways of the complement system seemed to be important in xenogeneic graft rejection. Among 416 DEPs of the cornea, NF‐κB1 and proteosomes (PSMD7, PSMA5, and PSMD3) seemed to be related with xenogeneic graft rejection. Additionally, oxidative phosphorylation and leukocyte activation‐related pathways are involved in rejection. Overall, our proteomic approach highlights the important role of NF‐κB1, proteosomes, oxidative phosphorylation, and leukocyte activation-related inflammation in the cornea, and the relevance of complement pathways of the aqueous humor as a predictive biomarker of xenogeneic rejection.
2022-05-20 | PXD031320 | Pride
Project description:Defining Cellular Population Dynamics in Advanced Prostate Cancer using Single-cell RNA Sequencing
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Project description:The human placenta is a dynamic and cellular heterogeneous organ, which is critical in fetomaternal homeostasis and the development of preeclampsia. Previous work has shown that placenta-derived cell-free RNA increases during pregnancy. We applied large-scale microfluidic single-cell transcriptomic technology to comprehensively characterize cellular heterogeneity of the human placentas and identified multiple placental cell-type–specific gene signatures. Analysis of the cellular signature expression in maternal plasma enabled noninvasive delineation of the cellular dynamics of the placenta during pregnancy and the elucidation of extravillous trophoblastic dysfunction in early preeclampsia.
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Project description:By leveraging single-cell/nuclei RNA sequencing, we generate the first single-cell transcriptome atlas of over 200,000 pig cells from 20 tissues/organs.
2022-01-21 | GSE193975 | GEO
Project description:Skin is the largest barrier organ with complex structure and function. We investigated the transcriptional dynamics of pig skin during development and aging at single-cell resolution. Using single-cell RNA sequencing, we profiled the transcriptomes of 443,529 skin cells derived from 30 individuals of 10 developmental time points staged between 56 days of gestation and 7 years old. Our analysis identified the dynamic changes in the cellular transcriptional profile of eight skin cell types at different developmental stages, exhibiting time-dependent skin cell heterogeneity.
2024-08-31 | GSE244532 | GEO
Project description:The bilaminar disc of early pig embryos closely mirrors that of humans making it a powerful model for studying gastrulation. Given the difficulties obtaining embryos in non-rodents, early cell-fate decisions during mammalian gastrulation remain ill-understood. Here we present a single-cell transcriptomic atlas of pig gastrulation and early organogenesis. We uncover the dynamics of cell fate emergence during pig peri-gastrulation and reveal conserved and species-specific transcriptional programs across different mammals. Combined with investigations in embryos and embryonic stem cells, we elucidate the spatial, molecular, and temporal events during definitive endoderm (DE) formation. We show that early FOXA2+ epiblast progenitors become DE without undergoing epithelial-to-mesenchymal transition, contrasting later emerging FOXA2/TBXT+ anterior primitive streak, which form node/notochord progenitors. We demonstrate that DE fate is driven by hypoblast-derived NODAL signalling, which is extinguished upon DE differentiation. These findings highlight the interplay between temporal and topological signalling during early cell fate decisions during mammalian gastrulation.
2023-10-05 | GSE236766 | GEO