Unknown,Transcriptomics,Genomics,Proteomics

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Comparative analysis of hESCs and iPSCs-derived hepatocyte-like cells reveals current drawbacks and possible strategies for improved differentiation

ABSTRACT: Two independent protocols for deriving HLCs from hESCs and iPSCs were adopted and further characterization included immunocytochemistry, real-time RT-PCR, and in vitro functional assays. Comparative microarray-based gene expression profiling was conducted on these cells and compared to the transcriptomes of human fetal liver and adult liver progenitors. HLCs derived from hESCs and hiPSCs showed significant functional similarities, similar expression of genes important for liver physiology and common pathways. However, specific differences between the two cell types could be observed. Total RNA obtained from undifferentiated hESCs, iPSCs, HLCs (hepatocyte-like cells)-derived from hESCs and iPSCs, fetal forskin fibroblasts and fetal liver.

ORGANISM(S): Homo sapiens

SUBMITTER: Justyna Jozefczuk

PROVIDER: E-GEOD-25744 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Comparative analysis of human embryonic stem cell and induced pluripotent stem cell-derived hepatocyte-like cells reveals current drawbacks and possible strategies for improved differentiation.

Jozefczuk Justyna J Prigione Alessandro A Chavez Lukas L Adjaye James J

Stem cells and development 20110124 7

Hepatocytes derived from human embryonic stem cells (hESCs) or induced pluripotent stem cells (iPSCs) could provide a defined and renewable source of human cells relevant for cell replacement therapies and toxicology studies. However, before patient-specific iPSCs can be routinely used for these purposes, there is a dire need to critically compare these cells to the golden standard--hESCs. In this study, we aimed at investigating the differences and similarities at the transcriptional level betw ...[more]

PMID: 21162674

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Project description:Background: Hepatocyte-like cells (HLCs) differentiated from induced pluripotent stem cells (iPSCs) have emerged as a promising cell culture model to study metabolism, biotransformation, viral infections and genetic liver diseases. However the derivation of iPSCs is restricted by ethical and procedural constraints. Furthermore, incomplete HLC differentiation remains a major challenge. iPSC may carry-on a tissue of origin dependent expression memory influencing iPSC differentiation into different cell types. If liver derived iPSCs (Li-iPSCs) maintain a liver specific gene expression profile is not known. It is also not known, if Li-iPSCs would allow the generation of more fully differentiated HLCs.Methods: Primary liver cells (PLCs) were expanded from liver needle biopsies and reprogrammed into Li-iPSCs using a non-integrative Sendai virus-based system. Li-iPSCs were differentiated into HLCs using established differentiation protocols. The HLC phenotype was characterized at the protein, functional and transcriptional level. RNA sequencing data were generated from the originating liver biopsies, the Li-iPSCs, fibroblast derived iPSCs, and differentiated HLCs, and used to characterize and compare their transcriptome profiles.Results: PLCs were obtained from small pieces of liver biopsies and could be reprogrammed into Li-iPSCs. Li-iPSCs indeed retain a liver specific transcriptional footprint. Li-iPSCs can be propagated to provide an unlimited supply of cells for differentiation into Li-HLCs. Similar to HLCs derived from fibroblasts, Li-HLCs could not be fully differentiated into hepatocytes. Relative to the originating liver, Li-HLCs showed lower expression of liver specific transcription factors and increased expression of genes involved in the differentiation of other tissues.Conclusions: PLCs and Li-iPSCs obtained from small pieces of human needle liver biopsies constitute a novel unlimited source for the production of HLCs. Despite the preservation of a liver specific gene expression footprint in Li-iPSCs, the generation of fully differentiated hepatocytes cannot be achieved with the current differentiation protocols.

Dataset Information

Comparative analysis of hESCs and iPSCs-derived hepatocyte-like cells reveals current drawbacks and possible strategies for improved differentiation

Publications

Comparative analysis of human embryonic stem cell and induced pluripotent stem cell-derived hepatocyte-like cells reveals current drawbacks and possible strategies for improved differentiation.

Similar Datasets

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