Single cell transcriptomics of partial hepatocyte reprogramming
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1198046 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:This study analyzes hepatocytes with Notch-induced reprogramming by single cell RNAseq compared to normal hepatocytes and biliary epithelial cells (BECs) in the normal liver.
2025-09-12 | GSE284235 | GEO
Project description:Partial pluripotent reprogramming has been reported to reverse some features of aging in mammalian cells and tissues. However, the impact of partial reprogramming on somatic cell identity programs and the necessity of individual pluripotency factors remain unknown. Here, we mapped trajectories of partial reprogramming in young and aged cells from multiple murine cell types using single cell transcriptomics to address these questions. We found that partial reprogramming restored youthful gene expression in adipogenic cells and mesenchymal stem cells but also temporarily suppressed somatic cell identity programs. We further screened Yamanaka Factor subsets and found that many combinations had an impact on aging gene expression and suppressed somatic identity, but that these effects were not tightly entangled. We also found that a partial reprogramming approach inspired by amphibian regeneration restored youthful gene expression in aged myogenic cells. Our results suggest that partial pluripotent reprogramming poses a neoplastic risk, but that restoration of youthful gene expression can be achieved with alternative strategies.
2022-02-28 | GSE197437 | GEO
Project description:Single-cell Spatial Transcriptomics Reveals Hepatocyte Metabolic Reprogramming in Fontan Associated Liver Disease
| PRJNA1366348 | ENA
Project description:Transcriptomics of mouse hepatocyte maturation and human hepatic reprogramming
| PRJNA717728 | ENA
Project description:Liver fibrosis is a strong predictor of long-term mortality in patients with non-alcoholic fatty liver disease; yet the mechanisms underlying the progression from the comparatively benign fatty liver state to advanced non-alcoholic steatohepatitis (NASH) and liver fibrosis are incompletely under-stood. Using a cell type-resolved genomics approach, we show that comprehensive alterations in hepatocyte genomic and transcriptional settings during NASH progression, led to a partial loss of hepatocyte identity. The hepatocyte reprogramming was under tight cooperative control of a net-work of NASH-activated transcription factors (TFs), as exemplified by Elf3 and Glis2. Indeed, Elf3 and Glis2 controlled hepatocyte identity and fibrosis-dependent hepatokine genes targeting disease-associated hepatic stellate cell (HSC) gene programs. Thus, interconnected TF networks not only promoted hepatocyte dysfunction, but also directed the intra-hepatic crosstalk with HSCs necessary for NASH and fibrosis progression implying molecular “hub-centered” targeting strategies to be superior to existing mono-target approaches as currently used in NASH therapy.
2021-07-13 | PXD025691 | Pride
Project description:Liver possesses robust regenerative ability, characterized by flexibility in the cellular source of regeneration based on the extent of the injury. After partial hepatectomy or minor injuries, hepatocytes, the primary liver cells, undergo self-duplication to replenish the liver mass. In contrast, when the damage is extensive, or hepatocyte proliferation is impaired, cholangiocytes contribute to hepatocyte recovery. This current paradigm of regenerative flexibility in the liver has been established for animals with little or no growth. However, the regenerative mechanisms during periods of growth in young animals remain unexplored. Here, we establish two new partial liver injury protocols in the zebrafish model of rapid growth during late larval stage and observe emergence of de novo hepatocytes in the presence of spared hepatocytes. Using single-cell RNA sequencing and lineage tracing, we identify cholangiocytes as the source of de novo hepatocytes. Our study offers a new perspective on the current paradigm of liver regenerating by proposing cholangiocyte-to-hepatocyte transdifferentiation as the default mechanism of hepatocyte recovery in late larval stage zebrafish.
2024-11-13 | GSE272484 | GEO
Project description:Partial pluripotent reprogramming in C2C12 myoblasts
| PRJNA810342 | ENA
Project description:The recovery of liver mass is mainly mediated by proliferation and enlargement of hepatocytes after partial hepatectomy. Studying the gene expression profiles of hepatocytes after partial hepatectomy will be helpful in exploring the mechanism of liver regeneration. We used microarrays to further highlight the regulatory role of hepatocyte in liver regeneration at gene transcription level.
2014-02-28 | GSE55434 | GEO
Project description:Spontaneous cellular reprogramming is rare, but has been observed in adult cells. This is most evident in the mammalian liver, where hepatocytes undergo physiological reprogramming to generate functional biliary epithelial cells (BECs) in response to injury. The underlying mechanisms driving this cell fate switch remain unclear, however. Here, we characterize epigenetic changes occurring during this transition at the single cell level, and show that reprogramming occurs synchronously and deterministically, though reprogrammed cells retain epigenetic hepatocyte memory. An in vivo CRISPR screen reveals the histone acetyltransferase-HBO1 functions as a critical barrier to hepatocyte reprogramming via acetylation of H3K14. HBO1 depletion accelerates BEC-specific chromatin remodeling and allows for the full resolution of the hepatocyte chromatin landscape. Mechanistically, HBO1 is recruited by the YAP to TEAD target sites to negatively its modulate chromatin-accessibility, DNA-binding, and transcriptional-output, thus acting as an epigenetic brake for YAP/TEAD function. Our work here delineates epigenetic trajectories of a physiological reprogramming process and identifies HBO1 as potential target for hepatocyte trans-differentiation therapeutic strategies.
2025-05-20 | GSE168828 | GEO
Project description:Partial reprogramming by expression of reprogramming factors (Oct4, Sox2, Klf4 and cMyc) for short periods of time restores a youthful epigenetic signature to aging cells and extends the lifespan of a premature aging mouse model. However, the effects of longer-term partial reprogramming in physiologically aging wild-type mice are unknown. Here, we have performed various long-term partial reprogramming regimens, including different onset timings, during physiological aging in different mouse strains. n=239 tissues from mice. The study involves different conditions (treated and untreated samples) and leads to 7 groups: 1) Black6 mouse +Doxocycline 2) 4 factor mouse+1 month of Doxocycline. 3) 4F mice+7month of Dox 4) 4F+10 months of Dox 5) 4F mice which are relatively old 6) B6 mice that are relatively old 7) 4F mice which are relatively young.
2021-12-10 | GSE190665 | GEO