Accession PRJCA008649
Title A two-step lineage reprogramming strategy to generate functionally competent human hepatocytes from fibroblasts
Relevance Medical
Data types Transcriptome or Gene expression
Raw sequence reads
Organisms Homo sapiens
Description Terminally differentiated cells can be generated by lineage reprogramming, which is, however, hindered by incomplete conversion with residual initial cell identity and partial functionality. Here, we demonstrate a new reprogramming strategy by mimicking the natural regeneration route, which permits generating expandable hepatic progenitor cells and functionally competent human hepatocytes. Fibroblasts were first induced into human hepatic progenitor-like cells (hHPLCs), which could robustly expand in vitro and efficiently engraft in vivo. Moreover, hHPLCs could be efficiently induced into mature human hepatocytes (hiHeps) in vitro, whose molecular identity highly resembles primary human hepatocytes (PHHs). Most importantly, hiHeps could be generated in large quantity and were functionally competent to replace PHHs for drug-metabolism estimation, toxicity prediction and hepatitis B virus infection modeling. Our results highlight the advantages of the progenitor stage for successful lineage reprogramming. This strategy is promising for generating other mature human cell types by lineage reprogramming.
Sample scope Multiisolate
Release date 2023-12-14
Grants
Agency program Grant ID Grant title
Ministry of Science and Technology of the People's Republic of China (MOST) 2017YFA0103000
National Natural Science Foundation of China (NSFC) 31730059
National Natural Science Foundation of China (NSFC) 31521004
National Natural Science Foundation of China (NSFC) 81670590
Ministry of Science and Technology of the People's Republic of China (MOST) 2015CB964703
Submitter Hongkui Deng (hongkui_deng@pku.edu.cn)
Organization Peking University
Submission date 2022-03-14

Project Data

Resource name Description
BioSample (32)  show -