Embedded Files
Chia-Ning Shen, Ph.D. 沈家寧 博士
Research Fellow
Genomics Research Center, Academia Sinica
中央研究院 基因體研究中心 研究員
Email: cnshen@gate.sinica.edu.tw
Reprogramming Cellular Identity for Liver Regenerative Medicine
End-stage liver diseases such as liver cirrhosis have become an increasingly prevalent disease. The liver transplantation is the only useful treatment for patients with end-stage liver diseases. However, the shortage of donor liver limit the potential use of liver transplantation to treat patients with end-stage liver diseases. Whether cell reprogramming strategies can be utilized to repair or to rejuvenate injured liver remains to be determined. Human induced pluripotent stem cells (iPSCs) can be generated from reprogramming of patient’s somatic cells. Recent work has shown that human iPSC-derived hepatocyte-like cells (iPSC-HLCs) have the potential to be used to treat End-stage liver diseases. However, the actual applicability is hampered by the limited availability of metabolically functioning hepatocytes derived from hiPSCs. In order to generate metabolically functioning hepatocytes, our recent progress has validated the expression of seven hepatic miRNAs including hsa-miR-664a-3p, hsa-miR-194-3p, hsa-miR-29c-5p, hsa-miR-4662a-5p, hsa-miR-885-5p, hsa-miR-126-5p, hsa-miR-122-3p during hepatic differentiation. Among these miRNAs, we revealed transfection of hsa-miR-4662a-5p can enhance metabolic gene expression and/or enzyme activity in HLCs and combination of hsa-miR-4662a-5p together with hsa-miR-126-5p, hsa-miR-122-3p further enhance the maturity of HLCs derived from ESCs and iPSCs.
Since the liver is an organ with an enormous capability of regeneration upon injury. Recent progress has further demonstrated hepatocyte reprogramming (dedifferentiation) contributes to regeneration process. We therefore tried to address the potential of direct-reprogramming mature hepatocytes to bipotential progenitors for the purpose of repairing liver injury. Initial efforts had demonstrated that periportal hepatocytes could be reprogrammed into Sox9-expressing progenitor cells in mice treated 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC). The further analysis revealed, in DDC-treated mice, N-methyl-PPIX produced from the breakdown of Cytochrome P450 and transported through ABCG2 could trigger induction of Sox-9 expression in hepatocyte reprogramming. We also confirmed the Sox9-expressing reprogrammed cells can therefore be used to replenish damaged hepatocytes. Collectively, our findings suggest both pluripotent and lineage reprogramming strategies possess the potency to development treatment for patients with end-stage liver diseases.
Position
2022-present Research Fellow/Professor, Genomics Research Center, Academia Sinica, Taiwan
2019-2022 Chief Executive Officer, Innovation Incubation Center, Biomedical Translation Research Center, Academia Sinica, Taiwan
Education
2002-2004 Research officer (postdoctoral scientist), Centre for Regenerative Medicine, University of Bath, United Kingdom.
1998-2002 Ph.D. Developmental Biology Program, Department of Biology and Biochemistry, University of Bath, United Kingdom.
1995-1997 MSc. Department of Biotechnology and Laboratory Science in Medicine, National Yang-Ming University, Taiwan
Expertise
Stem Cell Biology, Regenerative Medicine, 3D tissue imaging
Selected Publications
1. Lee et al., 2025. Human pancreatic duct-β-cell cluster in microscopic cystic change: panoramic-to-3D/Airyscan super-resolution imaging. Diabetes 74(5):734. DOI: 10.2337/db24-0824
2. Hsiao et al., 2023. Transparent tissue in solid state for 3D imaging: solvent-free and antifade. Nature Communications 14(1):3395. DOI: 10.1038/s41467-023-39082-4.
3. Chu et al., 2020. Generation of three induced pluripotent stem cell lines from type 2 diabetic patients with ocular complications. Stem Cell Res. 49:102109
4. Shen et al., 2019. Lymphatic vessel remodeling and invasion in pancreatic cancer progression. EBioMedicine 47:98-113.
Biosketch
Dr. Chia-Ning Shen is currently a Research fellow/Professor in the Genomics Research Center, Academia Sinica, Taiwan. Dr. Shen earned his PhD from Developmental Biology Program, Department of Biology and Biochemistry, University of Bath, United Kingdom in 2002. From 2002 to 2004, Dr. Shen worked as a research officer in the Centre for Regenerative Medicine in University of Bath. Dr. Shen came back to Taiwan and joined the Genomics Research Center of Academia Sinica in the summer of 2004. Dr. Shen's research interest primarily focuses on three fields, regenerative medicine, cancer biology and metabolism. Dr. Shen recently worked on investigating mechanisms involved in naturally occurring somatic cell reprogramming especially put efforts to identify the initial factors for neoplastic transformation in somatic cells. As of today, Dr. Shen has published 100 articles in world-renowned journals which have been cited more than 4700 times. Dr. Shen was also involved in the establishment of Taiwan Society for stem cell research (TSSCR) in 2005 aiming at providing opportunities for close interactions among stem cell researchers in Taiwan and with other international stem cell societies. Dr. Shen has been served as TSSCR president from 2017 to 2021 and then as the president for Taiwan Association for Cellular Therapy (TACT) from 2023 to 2024. To promote gene and cell therapeutic startup to develop. In July 2023, Dr. Shen & partners found CellTech Innovation Venture Studio.
Page updated
Report abuse