Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA234510 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR1107930.fastq.gz | Fastqsanger.gz | |||
| SRR1107931.fastq.gz | Fastqsanger.gz | |||
| SRR1107924.fastq.gz | Fastqsanger.gz | |||
| SRR1107925.fastq.gz | Fastqsanger.gz | |||
| SRR1107926.fastq.gz | Fastqsanger.gz |
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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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