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Single-cell transcriptional profiling of wildtype Rosa26(YFP) (Y) and Kras(G12D) p53(-/-) Rosa26-YFP (KPY) lung AT2 epithelial cells, AT2 organoids, and co-cultured mesenchymal cells with temporal resolution

ABSTRACT: The aim of this study was to examine the transcriptional dynamics of AT2 progenitor cells and their surrounding mesenchyme in lung adenocarcinoma across model systems, using temporal and single-cell resolution.

ORGANISM(S): Mus musculus

PROVIDER: GSE253461 | GEO | 2024/04/02

REPOSITORIES: GEO

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Single-cell transcriptional profiling of wildtype Rosa26(YFP) (Y) and Kras(G12D) p53(-/-) Rosa26-YFP (KPY) lung AT2 epithelial cells, AT2 organoids, and co-cultured mesenchymal cells with temporal resolution

Project description:Single-cell transcriptional profiling of wildtype Rosa26(YFP) (Y) and Kras(G12D) p53(-/-) Rosa26-YFP (KPY) lung AT2 epithelial cells, AT2 organoids, and co-cultured mesenchymal cells with temporal resolution

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Atp4b-Cre;Cdh1(fl/fl);Kras(LSL-G12D/+);Trp53(fl/fl);Rosa26(LSL-YFP/LSL-YFP) mouse stomach vs. Atp4b-Cre;Cdh1(fl/+);Kras(LSL-G12D/+);Trp53(fl/fl);Rosa26(LSL-YFP/LSL-YFP) mouse stomach microarray

Project description:We wished to investigate the role of E-cadherin loss in our mouse parietal cell/pre-parietal cell E-cadherin knock-out, p53 knock-out, oncogenic Kras induced model of gastric cancer. As such, we isolated RNA from stomach tissue from our E-cadherin knock-out model (Atp4b-Cre;Cdh1(fl/fl);Kras(LSL-G12D/+);Trp53(fl/fl);Rosa26(LSL-YFP/LSL-YFP)) and our E-cadherin heterozygous model (Atp4b-Cre;Cdh1(fl/+);Kras(LSL-G12D/+);Trp53(fl/fl);Rosa26(LSL-YFP/LSL-YFP)). We then performed a microarray on this stomach tissue from four independent mice of each genotype. Differentially expressed genes were identified and gene set overlap analysis was used to identify pathways enriched in one model over the other.

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Project description:The aim of the study was to investigate gene expression tumour progression of KRas*/MYC driven lung tumours from adenocarcinoma in situ to invasive disease.

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Project description:The experiment is a study of the effects of signal strength in the Ras pathway. In particular, we studied a gain-of-function mutant of Kras, KrasG12D. We generated these mutant mice and performed microarray analyses on RNA extracted from whole skin, comparing KrasG12D mice to wild-type mice, with three replicates of each.

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RNA-SEQ analysis of pancreatic ductal adenocarcinoma tumours in Pdx1-Cre;lsl-KRas[G12D] (KC), Pdx1-Cre;lsl-KRas[G12D];Rosa26-lsl-MYC[DM] (KMC), Pdx1-Cre;lsl-KRas[G12D];Rosa26-lsl-MYC[DM];c-Myc[fl/+] (KMC-Mycfl/+), and Pdx1-Cre;lsl-KRas[G12D];Rosa26-lsl-MYC[DM];Zbtb17[fl/fl] mice (KMC-Miz1fl/fl)

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Project description:AT2 cells are the resident progenitor cells in alveoli, capable of self-proliferation and differentiation into alveolar type I cells during homeostatic maintenance and tissue regeneration. The AT2 cell population is heterogenous. We identified a small subpopulation of AT2 cells that express high levels of CD44 (CD44hi) and display progenitor functions during alveoli homeostasis. To further analyze the heterogeneity of the AT2 cell population and characterize CD44hi AT2 cells, we performed single cell RNA-seq on the total AT2 cell population and CD44hi AT2 cells.

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