Human multi-energy stem cells in vitro liver differentiation key regulatory factors.

On May 31st, the international academic journal Stem Cell Reports published online the results of the collaborative research results of Ding Qiuyu and the Zhai Zhen Research Group of the Shanghai Institute of Nutrition and Health of the Chinese Academy of Sciences, Genetic and chemical screenings cys cys cynaHDA s key regulator in hepatic of human pluripotent stem cells.
the study identified human pluripotent stem cells (hPSCs) in vitro liver differentiation key regulatory factors, including histone deacetylase HDAC3, through large-scale genetic screening and compound screening.
liver-like cells (HLCs) from the source of in vitro targeted differentiation of human pluripotent stem cells (HLCs) are potentially important cell sources for liver disease simulations, toxicological tests, and liver transplanted donors.
the current HLCs are characterized by insufficient maturity and purity, which limits their applications in basic science and translational medicine.
in order to further optimize the in vitro directional differentiation system and promote the maturation and homogenization of liver cells, Ph.D. student Li Shuang and others tap into the Green Fluorescent Protein (Venus) expression box before the liver mature marker albumin (ALB) terminates, and establishes a human pluripotent stem cell reporting strain with mature liver lineage markers.
and on this basis, using CRISPR whole genome to knock out the slow virus library, large-scale genetic screening, identification of ATG7, RPS6KA2, HDAC3 and other genes involved in regulating human pluripotent stem cells in vitro liver differentiation.
also according to the screening of the regulatory gene and its related function tips, further targeted compound library screening, found that a histone deacetylase small molecular inhibitor CI-994 can significantly promote the directed differentiation of HLCs;
whole genome knockout slow virus library screening and small molecular compound bank screening confirmed that histone deacetylase HDAC3 is an important regulatory factor for liver differentiation, and further studies have found that HDAC3 can be combined with liver lineage key transcription factor HNF4 and other combinations to jointly regulate liver cell differentiation.
the study, using a combination of reporting gene cell strains, large-scale genetic screening and compound screening, established an efficient in vitro cell experimental system for studying the in vitro directional differentiation of liver cells of human pluripotent stem cells, and provided a universal and effective method for studying and optimizing hPSCs to other types of cell differentiation.
the study was completed by Li Shuang, research assistant Li Mushan and others under the guidance of researchers Ding Qiuxuan, Yu Zhen and Dr. Zhao Yongxu, and was also assisted by researchers Ying Hao, Fang Jing and Wang Hui of the Shanghai Institute of Nutrition and Health, Kiran Musunuru, professor of the University of Pennsylvania, and Ma Danjun, a professor at Dongguan University of Technology.
at the same time, the research has been supported by the national key research and development program, the Chinese Academy of Sciences stem cell pilot, the National Natural Science Foundation of China, etc., as well as the Shanghai Institute of Nutrition and Health public technology platform.
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