Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA345196 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR4340580_1.fastq.gz | Fastqsanger.gz | |||
| SRR4340580_2.fastq.gz | Fastqsanger.gz | |||
| SRR4340571_1.fastq.gz | Fastqsanger.gz | |||
| SRR4340571_2.fastq.gz | Fastqsanger.gz | |||
| SRR4340572_1.fastq.gz | Fastqsanger.gz |
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Project description:Pharmacological Induction of a Progenitor State for the Efficient Expansion of Primary Human Hepatocytes
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Project description:Pharmacological Induction of a Progenitor State for the Efficient Expansion of Primary Human Hepatocytes
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Project description:Hepatocytes hold significant promise for applications in drug screening, disease modeling, and clinical cell transplantation. Generating large amouts of hepatocyte in vitro for those application is still challenging. We have previously established a 5C medium for long-term culture and functional maintanace human primary hepatocytes (PHHs) in vitro. However, 5C condtion could not support hepatocyte expansion, which limited its application. In this study, we established a new hepatocyte expansion medium (NHEM) for efficient hepatocyte expansion, which turned the PHHs into hepatic progenitor-like cells (HPLCs). We also generated an optimized 6C condtion for HPLCs maturation. Overall, this study provide a new strategy to generate large amounts of hepatocytes in vitro.
2024-09-23 | GSE261965 | GEO
Project description:Hepatocytes hold significant promise for applications in drug screening, disease modeling, and clinical cell transplantation. Generating large amouts of hepatocyte in vitro for those application is still challenging. We have previously established a 5C medium for long-term culture and functional maintanace human primary hepatocytes (PHHs) in vitro. However, 5C condtion could not support hepatocyte expansion, which limited its application. In this study, we established a new hepatocyte expansion medium (NHEM) for efficient hepatocyte expansion, which turned the PHHs into hepatic progenitor-like cells (HPLCs). We also generated an optimized 6C condtion for HPLCs maturation. Overall, this study provide a new strategy to generate large amounts of hepatocytes in vitro.
2024-09-23 | GSE261962 | GEO
Project description:Cell fate can be directly converted between differentiated cells by lineage reprogramming, thus generating multiple cell types across developmental lineages. However, lineage reprogramming is hindered by incomplete cell-fate conversion with residual initial cell identity and partial functions compared with the native counterparts. Here, we develop a high-fidelity reprogramming strategy, by mimicking the natural cell-fate changing route, thus permitting the production of functionally competent human hepatocytes from another cell type. We first converted fibroblasts into plastic hepatic progenitor-like cells (hHPLCs) and chemically induced them into mature hepatocytes. The molecular identity of human induced hepatocytes (hiHeps) are suggested a terminally differentiated state, resembling primary human hepatocytes (PHHs). Functionally, hiHeps were competent to replace PHHs for equivalent drug-metabolizing activities, toxicity prediction and hepatitis B virus infection. Remarkably, the stably robust expansion of hHPLCs allowed large-scale generation of mature hepatocytes. Our results demonstrate the necessity of taking a reprogramming step for plastic progenitors for efficient cell-fate conversion. This strategy is promising for the generation of other mature human cell types.
2021-10-26 | GSE121860 | GEO
Project description:Cell fate can be directly converted between differentiated cells by lineage reprogramming, thus generating multiple cell types across developmental lineages. However, lineage reprogramming is hindered by incomplete cell-fate conversion with residual initial cell identity and partial functions compared with the native counterparts. Here, we develop a high-fidelity reprogramming strategy, by mimicking the natural cell-fate changing route, thus permitting the production of functionally competent human hepatocytes from another cell type. We first converted fibroblasts into plastic hepatic progenitor-like cells (hHPLCs) and chemically induced them into mature hepatocytes. The molecular identity of human induced hepatocytes (hiHeps) are suggested a terminally differentiated state, resembling primary human hepatocytes (PHHs). Functionally, hiHeps were competent to replace PHHs for equivalent drug-metabolizing activities, toxicity prediction and hepatitis B virus infection. Remarkably, the stably robust expansion of hHPLCs allowed large-scale generation of mature hepatocytes. Our results demonstrate the necessity of taking a reprogramming step for plastic progenitors for efficient cell-fate conversion. This strategy is promising for the generation of other mature human cell types.
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Project description:Induction of miRNA changes in primary human hepatocytes by valproic acid
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Project description:Induction of DNA methylation changes in primary human hepatocytes by valproic acid
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Project description:Induction of gene expression changes in primary human hepatocytes by valproic acid
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Project description:Currently, much effort is directed to the development of new cell sources for clinical therapy using cell fate conversion approaches by small molecules. Direct lineage reprogramming to a progenitor state has been reported in terminally differentiated rodent hepatocytes, yet remains a challenge in human hepatocytes. Human hepatocytes were isolated from healthy and diseased donor livers and reprogrammed into progenitor cells by two small molecules, A83-01 and CHIR99021 (AC), in the presence of EGF and HGF. The stemness properties of human chemically derived hepatic progenitors (hCdHs) were tested by standard in vitro and in vivo assays and transcriptome profiling. We developed a robust culture system for generating hCdHs with therapeutic potential. The use of HGF proved to be an essential determinant of fate conversion process. Based on functional evidence, activation of HGF/MET signal transduction system collaborated with A83-01 and CHIR99021 to allow a rapid expansion of progenitor cells through activation of ERK pathway. hCdHs expressed hepatic progenitor marker genes and proteins, and could self-renew for at least 10 passages while retaining normal karyotype and potential to differentiate into functional hepatocytes and biliary epithelial cells in vitro. RNASeq gene expression profiling confirmed transcriptional reprogramming of hCdHs toward a progenitor state and suppression of mature hepatocyte transcripts. Upon intrasplenic transplantation into immunocompromised mice with acute liver injury, hCdHs effectively repopulated damaged parenchyma. Our study is a first report of successful reprogramming of human hepatocytes to a population of proliferating bipotent cells with regenerative potential. hCdHs may provide a nove tool that permits expansion and genetic manipulation of patient-specific progenitors to study regeneration and repair of diseased liver.
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