Affymetrix profile of human liver progenitor cells
Ontology highlight
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.
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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.
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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 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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