Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1058155 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Mechanisms underlying human hepatocyte growth in development and regeneration are incompletely understood. In vitro, human fetal hepatocytes (FH) can be robustly grown as organoids, while adult primary human hepatocyte (PHH) organoids remain difficult to expand, suggesting different growth requirements between fetal and adult hepatocytes. Here, we characterize hepatocyte organoid outgrowth using temporal transcriptomic and phenotypic approaches. FHs initiate reciprocal transcriptional programs involving increased proliferation and repressed lipid metabolism upon initiation of organoid growth. We exploited these insights to design maturation conditions for FH organoids, resulting in acquisition of mature hepatocyte morphological traits and increased expression of functional markers. During PHH organoid outgrowth in the same culture condition, the adult transcriptomes initially mimic the fetal transcriptomic signatures, but PHHs rapidly acquire disbalanced proliferation-lipid metabolism dynamics, resulting in steatosis and halted organoid growth. IL6 supplementation, as emerged from the fetal dataset, and simultaneous activation of the metabolic regulator FXR, prevents steatosis and promotes PHH proliferation, resulting in improved expansion of the derived organoids. Single-cell RNA sequencing analyses reveal preservation of their fetal and adult hepatocyte identities in the respective organoid cultures. Our findings uncover mitogen requirements and metabolic differences determining proliferation of hepatocytes changing from development to adulthood.
2024-04-30 | GSE264261 | GEO
Project description:Mechanisms underlying human hepatocyte growth in development and regeneration are incompletely understood. In vitro, human fetal hepatocytes (FH) can be robustly grown as organoids, while adult primary human hepatocyte (PHH) organoids remain difficult to expand, suggesting different growth requirements between fetal and adult hepatocytes. Here, we characterize hepatocyte organoid outgrowth using temporal transcriptomic and phenotypic approaches. FHs initiate reciprocal transcriptional programs involving increased proliferation and repressed lipid metabolism upon initiation of organoid growth. We exploited these insights to design maturation conditions for FH organoids, resulting in acquisition of mature hepatocyte morphological traits and increased expression of functional markers. During PHH organoid outgrowth in the same culture condition, the adult transcriptomes initially mimic the fetal transcriptomic signatures, but PHHs rapidly acquire disbalanced proliferation-lipid metabolism dynamics, resulting in steatosis and halted organoid growth. IL6 supplementation, as emerged from the fetal dataset, and simultaneous activation of the metabolic regulator FXR, prevents steatosis and promotes PHH proliferation, resulting in improved expansion of the derived organoids. Single-cell RNA sequencing analyses reveal preservation of their fetal and adult hepatocyte identities in the respective organoid cultures. Our findings uncover mitogen requirements and metabolic differences determining proliferation of hepatocytes changing from development to adulthood.
2024-04-30 | GSE264260 | GEO
Project description:We model liver phenotypes associated with telomere dysfunction using DC patient-derived iPS cells and isogenic controls with CRISPR/Cas9-mediated homology-directed repair correction of the disease-causing DKC1 mutation. Differentiation of these cells into hepatocyte-like cells or hepatic stellate cells indicates that the parenchymal hepatocytes are primarily affected by telomere dysfunction. We develop an admixed hepatostellate organoid culture model which further reveals that mutant hepatocytes exert dominant effects on hepatic stellate cells regardless of stellate cell genotype. Hepatostellate organoids containing DKC1-mutant hepatocytes exhibit hyperplasia in both the hepatocyte compartment and, remarkably, in stellate cells. Moreover, mutant hepatocytes can induce hallmarks of stellate cell activation independently of stellate cell genotype. Interestingly, mutant hepatostellate organoids also contain off-target PLVAP+ endothelial cells reminiscent of scar-associated endothelium observed in non-DC cirrhosis patients.
2022-02-28 | GSE188987 | GEO
Project description:Induced pluripotent stem cell (iPSC) derived organoid systems provide models to study human organ development. Single-cell transcriptome sequencing enables highly-resolved descriptions of cell state heterogeneity within these systems and computational methods can reconstruct developmental trajectories. However, new approaches are needed to directly measure lineage relationships in these systems. Here we establish an inducible dual channel lineage recorder, iTracer, that couples reporter barcodes, inducible CRISPR/Cas9 scarring, and single-cell transcriptomics to analyze state and lineage relationships in iPSC-derived systems. This data set include the iTracer-perturb data of one cerebral organoid with simultaneous TSC2 perturbation and lineage recording.
2021-11-03 | E-MTAB-10971 | biostudies-arrayexpress
Project description:Induced pluripotent stem cell (iPSC) derived organoid systems provide models to study human organ development. Single-cell transcriptome sequencing enables highly-resolved descriptions of cell state heterogeneity within these systems and computational methods can reconstruct developmental trajectories. However, new approaches are needed to directly measure lineage relationships in these systems. Here we establish an inducible dual channel lineage recorder, iTracer, that couples reporter barcodes, inducible CRISPR/Cas9 scarring, and single-cell transcriptomics to analyze state and lineage relationships in iPSC-derived systems. This data set include the spatial iTracer data of three slices of one cerebral organoid measured by 10x Visium.
2021-11-03 | E-MTAB-10972 | biostudies-arrayexpress
Project description:Induced pluripotent stem cell (iPSC) derived organoid systems provide models to study human organ development. Single-cell transcriptome sequencing enables highly-resolved descriptions of cell state heterogeneity within these systems and computational methods can reconstruct developmental trajectories. However, new approaches are needed to directly measure lineage relationships in these systems. Here we establish an inducible dual channel lineage recorder, iTracer, that couples reporter barcodes, inducible CRISPR/Cas9 scarring, and single-cell transcriptomics to analyze state and lineage relationships in iPSC-derived systems. This data set include the iTracer data of two microdissected regions of one cerebral organoid.
2021-11-03 | E-MTAB-10973 | biostudies-arrayexpress
Project description:Hepatocytes are the predominant cell type in the liver and execute numerous essential biological functions. However, the crucial events and putative regulators during hepatocyte maturation require in-depth investigation. In this study, we performed single-cell and single-nucleus RNA-seq (scRNA-seq and snRNA-seq) to explore the developmental process of hepatocytes. We defined three maturation stages of postnatal hepatocytes, each of which establishes specific metabolic functions and exhibits distinct strategies for regulating proliferation. Hepatic zonation is gradually formed during hepatocyte maturation. The cells or nuclei of different ploidy exhibit zonation preferences in distribution, and asynchrony in the hepatocyte maturation pathway. In addition, combining gene regulatory network analysis and in vivo genetic manipulation, we identified critical maturation- and zonation-related transcription factors. This study not only delineates comprehensive transcriptomic profiles of hepatocyte maturation, but also presents a paradigm to identify functional genes in the development of hepatocyte maturation and zonation by combining genetic manipulation and measuring coordinates in a single-cell developmental trajectory.
2023-06-26 | GSE209749 | GEO
Project description:Cerebral organoids â three-dimensional cultures of human cerebral tissue derived from pluripotent stem cells â have emerged as models of human cortical development. However, the extent to which in vitro organoid systems recapitulate neural progenitor cell proliferation and neuronal differentiation programs observed in vivo remains unclear. Here we use single-cell RNA sequencing (scRNA-seq) to dissect and compare cell composition and progenitor-to-neuron lineage relationships in human cerebral organoids and fetal neocortex. Covariation network analysis using the fetal neocortex data reveals known and novel interactions among genes central to neural progenitor proliferation and neuronal differentiation. In the organoid, we detect diverse progenitors and differentiated cell types of neuronal and mesenchymal lineages, and identify cells that derived from regions resembling the fetal neocortex. We find that these organoid cortical cells use gene expression programs remarkably similar to those of the fetal tissue in order to organize into cerebral cortex-like regions. Our comparison of in vivo and in vitro cortical single cell transcriptomes illuminates the genetic features underlying human cortical development that can be studied in organoid cultures. 734 single-cell transcriptomes from human fetal neocortex or human cerebral organoids from multiple time points were analyzed in this study. All single cell samples were processed on the microfluidic Fluidigm C1 platform and contain 92 external RNA spike-ins. Fetal neocortex data were generated at 12 weeks post conception (chip 1: 81 cells; chip 2: 83 cells) and 13 weeks post conception (62 cells). Cerebral organoid data were generated from dissociated whole organoids derived from induced pluripotent stem cell line 409B2 (iPSC 409B2) at 33 days (40 cells), 35 days (68 cells), 37 days (71 cells), 41 days (74 cells), and 65 days (80 cells) after the start of embryoid body culture. Cerebral organoid data were also generated from microdissected cortical-like regions from H9 embryonic stem cell derived organoids at 53 days (region 1, 48 cells; region 2, 48 cells) or from iPSC 409B2 organoids at 58 days (region 3, 43 cells; region 4, 36 cells).
2015-12-07 | E-GEOD-75140 | biostudies-arrayexpress
Project description:Trellis Single-Cell Screening Reveals Stromal Regulation of Patient-Derived Organoid Drug Responses
| PRJNA999180 | ENA