Affymetrix profile of human liver progenitor cells
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE57812 | GEO | 2015/05/01
SECONDARY ACCESSION(S): PRJNA248310
REPOSITORIES: GEO
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Project description:Human liver progenitor cells (LPCs) show therapeutic potential, however, their in vitro culture results in inadequate function and phenotypic instability reflecting incomplete understanding of in vivo processes. Foetal LPCs capable of differentiation to a hepatocyte phenotype were isolated and mRNA expression profiling carried out using Affymetrix HGU133plus2 microarrays. This was compared to profiles from mature human hepatocytes and human embryonic stem cells undergoing hepatocytic differentiation. Foetal LPCs exhibit a distinct molecular profile consistent with a stem cell signature, cell division, and some liver-specific functions. 9 independent samples of second trimester liver progenitor cells were profiled along with 3 independent mature hepatocyte samples and 3 each of embryonic stem cells at day 9 and day 17 of differentiation to hepatocyte like cells.
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Project description:Human liver progenitor cells (LPCs) show therapeutic potential, however, their in vitro culture results in inadequate function and phenotypic instability reflecting incomplete understanding of in vivo processes. Foetal LPCs capable of differentiation to a hepatocyte phenotype were isolated and mRNA expression profiling carried out using Exiqon miRCURY microarrays. This was compared to profiles from mature human hepatocytes. Foetal LPCs exhibit a distinct miRNA profile consistent with a stem cell signature, cell division, and some liver-specific functions. 3 independent samples of second trimester liver progenitor cells were prolfiled along with 3 independent mature hepatocyte samples.
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Project description:Human liver progenitor cells (LPCs) show therapeutic potential, however, their in vitro culture results in inadequate function and phenotypic instability reflecting incomplete understanding of in vivo processes. Foetal LPCs capable of differentiation to a hepatocyte phenotype were isolated and mRNA expression profiling carried out using Exiqon miRCURY microarrays. This was compared to profiles from mature human hepatocytes. Foetal LPCs exhibit a distinct miRNA profile consistent with a stem cell signature, cell division, and some liver-specific functions.
2015-05-01 | GSE57833 | GEO
Project description:Embryonic stem cells (ESCs) have the potential to yield new liver cells for regenerative medicine. However it has been challenging to generate homogeneous ESC-derived human liver populations capable of engrafting in vivo and ameliorating liver failure. To overcome this challenge, we define extrinsic signals regulating six consecutive stages of human liver development, including patterning of endoderm into foregut, liver bud specification, and segregation of hepatocyte vs. biliary fates. This knowledge enabled differentiation of human ESCs into 89% pure AFP+HNF4A+TBX3+ liver bud progenitors and subsequently, a >77% uniform ALB+ hepatocytic population. ESC-derived ALB+ human hepatocytic cells engrafted the damaged livers of Fah-/- mice, improving overall mouse survival and reducing liver damage. Interestingly, certain signals that matured hESC-derived hepatocytic cells also sustained primary adult hepatocytes in vitro for one week. Collectively we demarcate extrinsic signaling, mRNA and surface marker dynamics during human liver development, enabling the generation of engraftable liver cells from ESCs.
2018-02-20 | GSE98324 | GEO
Project description:Increasing evidence provide support that the mammalian liver contains stem/progenitor cells, but their molecular phenotype, embryological derivation, cell biology as well as of their role in the liver cell turnover and regeneration remain to be further clarified. We report the isolation, characterization and reproducible establishment in line of a resident liver stem cell (RLSC) with immunophenotype and differentiative potential distinct from other previously reported liver precursor/stem cells. RLSCs, derived from foetal and neonatal murine livers as well as from immortalized hepatocytic MMH lines and established in lines, are Sca+, CD34-, CD45-, alfa-fetoprotein+, albumin-. This immunophenotype suggests a non-haematopoietic origin. RLSCs transcriptional profile, defined by microArray technology, highlighted the expression of a broad spectrum of âplasticity-related genesâ and âdevelopmental genesâ suggesting a multi-differentiative potential. RLSCs, indeed, spontaneously differentiate into hepatocytes and cholangiocytes and, when cultured in appropriate conditions, into mesenchymal and neuro-ectodermal cell lineages, such as osteoblasts/osteocytes, chondrocytes, astrocytes and neuronal cells. RLSCs capability to spontaneously differentiate into hepatocytes, the lack of albumin expression and the broad differentiative potentiality locate them in a pre-hepatoblast/liver precursor cells hierarchical position. In conclusion, RLSCs may provide an useful tool to improve liver stem cell knowledge and to assess new therapeutic approaches for liver diseases. Experiment Overall Design: We compared the gene expression profile of a RLSC line to that of the previously characterised hepatocytic differentiated cell line MMH-D3 (ref Amicone), using Affymetrix Mouse430_2 GeneChip array.
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Project description:Increasing evidence provide support that the mammalian liver contains stem/progenitor cells, but their molecular phenotype, embryological derivation, cell biology as well as of their role in the liver cell turnover and regeneration remain to be further clarified. We report the isolation, characterization and reproducible establishment in line of a resident liver stem cell (RLSC) with immunophenotype and differentiative potential distinct from other previously reported liver precursor/stem cells. RLSCs, derived from foetal and neonatal murine livers as well as from immortalized hepatocytic MMH lines and established in lines, are Sca+, CD34-, CD45-, alfa-fetoprotein+, albumin-. This immunophenotype suggests a non-haematopoietic origin. RLSCs transcriptional profile, defined by microArray technology, highlighted the expression of a broad spectrum of “plasticity-related genes” and “developmental genes” suggesting a multi-differentiative potential. RLSCs, indeed, spontaneously differentiate into hepatocytes and cholangiocytes and, when cultured in appropriate conditions, into mesenchymal and neuro-ectodermal cell lineages, such as osteoblasts/osteocytes, chondrocytes, astrocytes and neuronal cells. RLSCs capability to spontaneously differentiate into hepatocytes, the lack of albumin expression and the broad differentiative potentiality locate them in a pre-hepatoblast/liver precursor cells hierarchical position. In conclusion, RLSCs may provide an useful tool to improve liver stem cell knowledge and to assess new therapeutic approaches for liver diseases. Keywords: cell type comparison
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Project description:As MLL-rearranged infant leukaemia is known to initiate in utero, we sought to identify developemntal genes expressed in foetal cells that may aid leukaemogenesis. Bulk RNA-Seq was therefore carried out on mouse and human foetal liver blood progenitors (lymphoid-primed multipotent progenitors [LMPPs] and haematopoietic stem cells/ multipotent progenitor cells [HSC/MPPs]) and compared with the same cell types isolated from developmentally later human cord blood and mouse adult bone marrow.
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Project description:The loss of cone photoreceptor cells, which are critical for optimal daylight vision, have the great impact on vision during retinal degenerations. Retinal differentiation of human induced pluripotent stem cell (hiPSC) sources could provide a renewable source of cone photoreceptors towards developing a cone cell replacement therapy to treat blindness. Demonstration of comparable gene expression profiles between human foetal and stem cell-derived cones at equivalent stages is required to progress the cell transplantation approach into the patient, as it is hypothesised stem cell-derived cones are required to show high levels of developmental recapitulation of the in vivo generated cones. In this study, the AAV2/9.pR2.1.GFP reporter was used to specifically label L/M-opsin cone photoreceptors in human foetal retinal samples, obtained from the MRC-Wellcome Trust Human Developmental Biology Resource, at a range of developmental stages. The L/M-opsin cone population represent the majority cone cell types in the adult human retina and are the only photoreceptors present within the fovea. Using fluorescence activated cell sorting, L/M-opsin GFP+ cones and GFP- retinal populations, alongside total foetal retinal samples containing all retinal cell tytpes, were isolated and processed for bulk RNA sequencing and downstream comparative analysis. Using DESeq2 differential gene expression analyses, statistically significant genes enriched within the GFP+ human foetal LM-opsin cone populations were determined which led to the identification of a cone enriched gene signature of human L/M-opsin cone photoreceptors. The AAV2/9.pR2.1.GFP reporter was applied to hiPSC-derived retinal cultures to isolate and process cone-like cell populations for RNA sequencing using the same strategy developed within the human foetal retina. Applying the cone enriched gene signature to the transcriptome of hiPSC-derived GFP+ samples at equivalent developmental stages revealed some expression similarities in genes found to be enriched within the late foetal L/M-opsin cone photoreceptors. This analysis overall revealed an intermediate stage of cone differentiation was achieved within the hiPSC-derived samples and the comparison to human foetal L/M-opsin gene express profiles suggesting further differentiation of hiPSC-derived sample is required.
2018-04-20 | E-MTAB-6057 | biostudies-arrayexpress
Project description:The cellular source for hepatocyte transplantation and liver regeneration in chronically hepatic diseases is a fundamental topic in liver biology. A successful therapeutic approach based on a benificial stem/progenitor cells would involve replacing damaged cells or restoring homeostasis to the areas that underlie the fibrotic response. This study aims to isolate and culture hepatocyte and non-parenchymal cells derived liver progenitor-like cells (HepLPCs and NPC-LPCs) to identify a beneficial cell sources for cell-based therapy against chronic liver injury. Two types of lineage tracing models including tdTomato mice with AAV8-TBG-Cre and AlbCreERT/R26GFP were purified for hepatocytes and non-parenchymal cells respectively, and cultured for transition to progenitor-like cells (LPCs) in TEM. The differences between them were clarified by RNA sequencing, suggesting that HepLPCs retaining basal levels of hepatic function and transcription factors (TFs), including Foxa3. Organoids and 3D hepatic spheroids culturing systems were used for further analysis of bile duct and hepatic functioning diversity. When transplanting in mice with CCL4 treatment, HepLPCs displayed the characteristics of TFs regulatory reactivation and physiological balance restoration, resulting in a significant improvement in liver fibrosis compared with NPC-LPCs, which are crucial for liver regeneration in the treatment of patients with a broad range of hepatic fibrosis.
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