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| Status |
Public on Sep 02, 2019 |
| Title |
A novel reprogramming strategy to generate functionally competent human hepatocytes |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
Non-coding RNA profiling by high throughput sequencing
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| Summary |
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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| Overall design |
Total of 47 samples were analyzed, which included human embryonic fibroblasts, primary human hepatocytes, human hepatic progenitor-like cells, human induced hepatocytes and human fetal liver cells.Global transcriptional profiles of these cells were analyzed by RNA-seq.
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| Contributor(s) |
Xie B, Sun D, Deng H |
| Citation(s) |
31270412 |
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| Submission date |
Mar 26, 2018 |
| Last update date |
Jun 15, 2020 |
| Contact name |
Bingqing Xie |
| E-mail(s) |
bingqingxie0503@126.com
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| Phone |
+86 15600604841
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| Organization name |
Peking University
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| Street address |
Peking University, No.5 Yiheyuan Road Haidian District, Beijing, P.R.China
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| City |
Beijing |
| ZIP/Postal code |
100871 |
| Country |
China |
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| Platforms (2) |
| GPL16791 |
Illumina HiSeq 2500 (Homo sapiens) |
| GPL20301 |
Illumina HiSeq 4000 (Homo sapiens) |
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| Samples (47)
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| Relations |
| BioProject |
PRJNA445694 |
| SRA |
SRP136469 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE112330_genes.counts_tracking_hiHeps.csv.gz |
1.2 Mb |
(ftp)(http) |
CSV |
| GSE112330_miRNA_raw_count_180825.csv.gz |
33.4 Kb |
(ftp)(http) |
CSV |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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