Superior Expansion of Zone 2 Hepatocytes in Pregnancy
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE221375 | GEO | 2023/11/30
REPOSITORIES: GEO
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Project description:The liver is organized into zones in which hepatocytes express different metabolic enzymes. The cells most responsible for liver repopulation and regeneration remain undefined because fate-mapping has only been performed on a few hepatocyte subsets. Fourteen mouse fate mapping strains were used to systematically compare distinct subsets of hepatocytes. During homeostasis, cells from both periportal zone 1 and pericentral zone 3 contracted in number, whereas cells from midlobular zone 2 expanded in number. These cells, which are sheltered from common injuries, also contributed to regeneration after pericentral and periportal injuries. Zone 2 repopulation was driven by the IGFBP2-mTOR-CCND1 axis. Hence, different regions of the lobule exhibit differences in their contributions to hepatocyte turnover, and zone 2 is the primary source of new hepatocytes during homeostasis and regeneration.
2022-12-01 | GSE162713 | GEO
Project description:Human hepatocytes differ in gene expression and function across the hexagonal lobules of the tissue microarchitecture, a phenomenon referred to as liver zonation. Hepatocytes also display intra-lobular differences in cell size, but to what extent zonal expression and function correlate with cell size in isolated human hepatocytes is not entirely clear. Here, we first used our accumulated experience of nearly 100 hepatocyte isolations to assess the impact of donor background and process parameters on hepatocyte quality. We observed substantial inter-batch variability in cell size distributions and a tendency for overall cell size to affect the outcome of hepatocyte isolation and cryopreservation. We further separated cells into different size fractions and analyzed them with label-free quantitative proteomics. This showed that protein abundances in different hepatocyte size fractions recapitulated the in vivo expression patterns of well-known zonal markers. We also found that proteins with sequential enrichment across fractions largely represented biological processes with known zonal specificity. This was confirmed by differences in the metabolic activity of zonated CYP enzymes. Altogether, our results show that hepatocyte size corresponds to zonal origin, and that our size fractionation approach can be used to study zone-specific liver functions in vitro.
2021-01-26 | PXD013142 | Pride
Project description:Organ size is maintained by the controlled proliferation of distinct cell populations. In the mouse liver, hepatocytes in the midlobular zone that are positive for cyclin D1 (CCND1) repopulate the parenchyma at a constant rate to preserve liver mass. Here, we investigated how hepatocyte proliferation is supported by hepatic stellate cells (HSCs), pericytes that are in close proximity to hepatocytes. We used T cells to ablate nearly all HSCs in the murine liver, enabling the unbiased characterization of HSC functions. In the normal liver, complete loss of HSCs persisted for up to 10 weeks and caused a gradual reduction in liver mass and in the number of CCND1+ hepatocytes. We identified neurotrophin-3 (Ntf-3) as an HSC-produced factor that induced the proliferation of midlobular hepatocytes through the activation of tropomyosin receptor kinase B (TrkB). Treating HSC-depleted mice with Ntf-3 restored CCND1+ hepatocytes in the midlobular region and increased liver mass. These findings establish that HSCs form the mitogenic niche for midlobular hepatocytes and identify Ntf-3 as a hepatocyte growth factor.
2023-06-27 | GSE211370 | GEO
Project description:Primary human hepatocytes (PHH) are an essential tool for modeling drug metabolism and liver disease. However, variable plating efficiencies, short lifespan in culture and resistance to genetic manipulation have limited their use. Here we show that retrorsine improves human hepatocyte repopulation of chimeric mice to levels where poor donor PHH can be isolated for ex vivo cultures. Mouse-passaged (mp)PHH cultures overcome the marked donor-to-donor variability of cryopreserved PHH and remain functional for months, as demonstrated by metabolic assays and infection with hepatitis B virus and Plasmodium falciparum. mpPHH can be efficiently genetically modified in culture, mobilized and then re-cultured as spheroids or re-transplanted to create highly humanized mice carrying a genetically altered hepatocyte graft. Together, these advances provide flexible tools for studying human liver disease and evaluating hepatocyte-targeted gene therapy approaches
2019-12-02 | GSE130219 | GEO
Project description:This SuperSeries is composed of the following subset Series: GSE38696: Gene expression in mouse germinal center light zone and dark zone B cells GSE38697: Gene expression in human germinal center light zone and dark zone B cells Keywords: Expression profiling by array Refer to individual Series
2012-06-13 | E-GEOD-38712 | biostudies-arrayexpress
Project description:Background & Aims: Mouse models of lineage tracing have helped to describe the important
subpopulations of hepatocytes responsible for liver regeneration. However, conflicting results have been obtained from different models. Here we aimed to reconcile these conflicting reports by repeating a key lineage tracing study from pericentral hepatocytes and characterised this Axin2CreERT2 model in detail.
Methods: We performed detailed characterisation of the labelled population in the Axin2CreERT2 model. We lineage traced this cell population, quantifying the labelled population over 1 year and performed in depth phenotypic comparison including transcriptomics, metabolomics and analysis of protein through immunohistochemistry of Axin2CreERT2 mice to WT counterparts.
Results: We find that after careful definition of a baseline population there is marked differences in labelling between male and female mice. Upon induced lineage tracing there was no expansion of the labelled hepatocyte population in Axin2CreERT2 mice. We find substantial evidence of disrupted homeostasis in Axin2CreERT2 mice. Offspring are born with sub-Mendelian ratios and adult mice have perturbations of hepatic Wnt/b-catenin signalling and related metabolomic disturbance.
Conclusions: We find no evidence of predominant expansion of the pericentral hepatocyte population during liver homeostatic regeneration. Our data highlight the importance of detailed preclinical model characterisation and the pitfalls which may occur when comparing across sexes and backgrounds of mice and the effects of genetic insertion into native loci.
2023-01-18 | MSV000091082 | MassIVE
Project description:We analyzed differences in placental gene expressions. We examined the mRNA expression profile in placental labyrinth zone from normal pregnant mice, and PAH mice with different Nrf2 expressions (WT, Nrf2 Knockout [KO], Keap1 Knockdown [KD])
2017-01-01 | GSE76669 | GEO
Project description:To elucidate molecular features of the cells of Sub-ventricular Zone (SVZ), their progeny at each differentiation stage, and surrounding cells in SVZ under blast wave-induced changes, cells were profiled from matched SVZ of 3 mice that had received blast injury and 3 controls（The controls sequencing profile can be assessed in GEO at GSM5938054）.Cell type specific gene expression responding to (blast-related traumatic brain injury, bTBI) were revealed, some of which were closely associated with pathogenesis post-injury. Furthermore, the diverse cell to cell interaction networks uncovered an array of cellular processes under bTBI. Our gene expression atlas provides extensive resources for future researches regarding bTBI induced pathogenesis, its therapeutic interventions or diagnostic tests.
2022-06-28 | GSE207078 | GEO
Project description:Microarrays of gene expression in human germinal center light zone and dark zone B cells sorted according to the expression of cell surface molecules CD83 and CXCR4 We used microarray data to identify genes differentially expressed by B cells in the light and dark zones of germinal centers from human tonsil specimens. Germinal center B cells (CD19+CD38+IgD-) were sorted from pediatric tonsil discard specimens into light zone (CXCR4hi/CD83lo) and dark zone (CXCR4lo/CD83hi) populations, from which RNA was extracted
2012-06-13 | E-GEOD-38697 | biostudies-arrayexpress
Project description:Microarrays of gene expression in mouse germinal center light zone and dark zone B cells sorted according to the expression of cell surface molecules CD83 and CXCR4 We used microarray data to identify genes differentially expressed by B cells in the light and dark zones of germinal centers from mouse skin-draining lymph nodes 12 days after subcutaneous immunization with NP-OVA in alum. Germinal center B cells (B220+CD38-CD95+) were sorted from immunized mouse lymph nodes into light zone (CXCR4hi/CD83lo) and dark zone (CXCR4lo/CD83hi) populations, from which RNA was extracted
2012-06-13 | E-GEOD-38696 | biostudies-arrayexpress