Chromatin openin profiles in mouse ApcDeltaHep or wt hepatocytes
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE211930 | GEO | 2023/12/31
REPOSITORIES: GEO
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Project description:We analyzed chromatin opening in hepatocytes isolated from Apclox/loxlivers, after injection of adenovirus Ad5 -Cre-GFP and sorting on the basis of GFP signal at day 6, 15 and 21 post-injection. Our aims was to study the impact of an aberrant beta-catenin activation on chromatin opening in hepatocytes during the early steps of liver tumorigenesis.
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Project description:Adult liver has enormous regenerative capacity as it can regenerate after losing two-thirds of its mass while sustaining essential metabolic functions. How the liver balances dual demands for increased proliferative activity with maintenance of organ function is unknown, but essential to prevent liver failure. Using partial hepatectomy (PHx) in mice to model liver regeneration, we integrated single-cell RNA and ATAC sequencing to map state transitions in ~ 13,000 hepatocytes at single-cell resolution as livers regenerated, and validated key findings with immunohistochemistry, to uncover how the organ regenerates hepatocytes while simultaneously fulfilling its vital tissue-specific functions. After PHx, hepatocytes rapidly and transiently diversified into multiple distinct populations with distinct functional bifurcation: some retained the chromatin landscapes and transcriptomes of hepatocytes in undamaged adult livers while others transitioned to acquire chromatin landscapes and transcriptomes of fetal hepatocytes. Injury-related signaling pathways known to be critical for regeneration were activated in transitioning hepatocytes and the most fetal-like hepatocytes exhibited chromatin landscapes that were enriched with transcription factors regulated by those pathways.
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Project description:Adult liver has enormous regenerative capacity as it can regenerate after losing two-thirds of its mass while sustaining essential metabolic functions. How the liver balances dual demands for increased proliferative activity with maintenance of organ function is unknown, but essential to prevent liver failure. Using partial hepatectomy (PHx) in mice to model liver regeneration, we integrated single-cell RNA and ATAC sequencing to map state transitions in ~ 13,000 hepatocytes at single-cell resolution as livers regenerated, and validated key findings with immunohistochemistry, to uncover how the organ regenerates hepatocytes while simultaneously fulfilling its vital tissue-specific functions. After PHx, hepatocytes rapidly and transiently diversified into multiple distinct populations with distinct functional bifurcation: some retained the chromatin landscapes and transcriptomes of hepatocytes in undamaged adult livers while others transitioned to acquire chromatin landscapes and transcriptomes of fetal hepatocytes. Injury-related signaling pathways known to be critical for regeneration were activated in transitioning hepatocytes and the most fetal-like hepatocytes exhibited chromatin landscapes that were enriched with transcription factors regulated by those pathways.
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Project description:Adult liver has enormous regenerative capacity as it can regenerate after losing two-thirds of its mass while sustaining essential metabolic functions. How the liver balances dual demands for increased proliferative activity with maintenance of organ function is unknown, but essential to prevent liver failure. Using partial hepatectomy (PHx) in mice to model liver regeneration, we integrated single-cell RNA and ATAC sequencing to map state transitions in ~ 13,000 hepatocytes at single-cell resolution as livers regenerated, and validated key findings with immunohistochemistry, to uncover how the organ regenerates hepatocytes while simultaneously fulfilling its vital tissue-specific functions. After PHx, hepatocytes rapidly and transiently diversified into multiple distinct populations with distinct functional bifurcation: some retained the chromatin landscapes and transcriptomes of hepatocytes in undamaged adult livers while others transitioned to acquire chromatin landscapes and transcriptomes of fetal hepatocytes. Injury-related signaling pathways known to be critical for regeneration were activated in transitioning hepatocytes and the most fetal-like hepatocytes exhibited chromatin landscapes that were enriched with transcription factors regulated by those pathways.
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Project description:We analyzed the expression of RNAs and microRNAs in hepatocytes isolated from ApcDeltaHep livers, either ROSA26 or deleted for the b-catenin binding site upstream of the DLK1/DIO3 locus by Crispr/Cas9 (DLK1DeltaWRE). We thus explored if editing of this regulatory site impaired the expression of the entire locus and which signaling pathways were modulated.
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Project description:We generated chimeric mice with livers that were predominantly repopulated with human hepatocytes. Hepatocytes were isolated from the chimeric mouse livers and their gene expressions were compared with hepatocytes isolated from normal human livers . Cluster and principal components analyses showed that gene expression profiles of hepatocytes from the chimeric mice and those from normal human livers were extremely closed. Additionally, we performed microarray experiments to examine gene expression in human tissues. This data was used for comparison with hepatocytes. A total of 22 tissues (bone marrow, cerebellum, colon, cortex, fetal brain, heart, kidney, liver, lung, pancreas, prostate, salivary gland, skeletal muscle, small intestine, spinal cord, spleen, stomach, testes, thymus, thyroid, trachea and uterus) were examined. The chimeric mice were generated by transplantation of 2 different donor hepatocytes. Hepatocytes were isolated from the mouse livers and normal human livers, and their cDNAs were used for microarray analysis. Total RNA isolated from human tissues and cell cultures were labeled and hybridized to the GeneChip Human Genome U133 Plus 2.0 Array according to the manufacturer's protocol.
2012-11-27 | E-GEOD-33846 | biostudies-arrayexpress