School of Basic Medical Sciences, MOE Engineering Research Center of Regenerative Medicine, State Key Laboratory of Natural and Biomimetic Drugs, Peking University Health Science Center and the MOE Key Laboratory of Cell Proliferation and Differentiation, College of Life Sciences, Peking-Tsinghua Center for Life Sciences, Peking University, Beijing, China.
Department of Biomedical Informatics, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China.
Cell Prolif. 2024 Feb;57(2):e13540. doi: 10.1111/cpr.13540. Epub 2023 Oct 9.
Derivation of human hepatocytes from pluripotent stem cells in vitro has important applications including cell therapy and drug discovery. However, the differentiation of pluripotent stem cells into hepatocytes in vitro was not well recapitulated the development of liver. Here, we developed a differentiation protocol by mimicking the two-stage development of hepatoblasts, which permits the efficient generation of hepatic progenitor cells from chemically induced pluripotent stem cells (hCiPSCs). Single-cell RNA sequencing (scRNA-seq) indicates the similarity between hepatoblasts differentiated in vitro and in vivo. Moreover, hCiPSC-derived hepatic progenitor cells can further differentiate into hepatocytes that are similar to primary human hepatocytes with respect to gene expression and key hepatic functions. Our results demonstrate the feasibility of generating hepatic progenitor cells and hepatocytes from hCiPSCs with high efficiency and set the foundation for broad translational applications of hCiPSC-derived hepatocytes.
体外诱导多能干细胞分化为成熟肝细胞具有重要的应用价值，包括细胞治疗和药物发现。然而，体外多能干细胞向肝细胞的分化并不能很好地模拟肝脏的发育过程。在此，我们通过模拟肝前体细胞的两阶段发育过程开发了一种分化方案，该方案可从化学诱导的多能干细胞（hCiPSCs）中高效产生肝祖细胞。单细胞 RNA 测序（scRNA-seq）表明，体外分化的肝前体细胞与体内分化的肝前体细胞具有相似性。此外，hCiPSC 来源的肝祖细胞可进一步分化为与原代人肝细胞在基因表达和关键肝功能方面相似的肝细胞。我们的研究结果表明，从 hCiPSCs 中高效产生肝祖细胞和肝细胞是可行的，并为 hCiPSC 来源的肝细胞的广泛转化应用奠定了基础。
