Generation of Functional Hepatocytes from Human Adipose-Derived MYC(+) KLF4(+) GMNN(+) Stem Cells Analyzed by Single-Cell RNA-Seq Profiling.
Generation of Functional Hepatocytes from Human Adipose-Derived MYC(+) KLF4(+) GMNN(+) Stem Cells Analyzed by Single-Cell RNA-Seq Profiling.
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DOI：
10.1002/sctm.17-0273
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发表时间：
2018-11
影响因子：
6
通讯作者：
Zhao RC
中科院分区：
文献类型：
--
作者：
Li H;Zhu L;Chen H;Li T;Han Q;Wang S;Yao X;Feng H;Fan L;Gao S;Boyd R;Cao X;Zhu P;Li J;Keating A;Su X;Zhao RC
细胞移植对终末期肝病有相当大的希望，但确定合适的可移植细胞类型一直存在问题。在这里，我们描述了一种新型的间充质干细胞（MSC）从人类脂肪组织。这些细胞与先前报道的MSC不同，它们处于常染色质状态，具有表观遗传多能性，并表达多能标记物MYC，KLF 4和GMNN。大多数与胚层特化相关的基因被H3 K4 me 3修饰或被H3 K4 me 3和H3 K27 me 3共修饰。我们将这种新型的MSC命名为成人多能脂肪源性干细胞（M-ADSC）。使用四步非病毒系统，M-ADSC可以被有效地诱导为肝细胞样细胞，其表达肝细胞标志物、药物代谢酶和转运蛋白，以及其他基本功能特性，包括白蛋白（ALB）分泌、糖原储存、解毒、低密度脂蛋白摄入和脂质积累。在体内，M-ADSC衍生的成肝细胞和肝细胞都可以形成血管化的肝样组织，分泌ALB并表达代谢酶。使用单细胞RNA-seq来研究这种转化中的重要阶段。M-ADSC可以在诱导前阶段转化为功能多能状态，而无需经历重编程过程。我们的发现为细胞发育和转化的机制提供了重要的见解。干细胞转化医学2018;7：792-805
Cell transplantation holds considerable promise for end‐stage liver diseases but identifying a suitable, transplantable cell type has been problematic. Here, we describe a novel type of mesenchymal stem cells (MSCs) from human adipose tissue. These cells are different from previously reported MSCs, they are in the euchromatin state with epigenetic multipotency, and express pluripotent markers MYC, KLF4, and GMNN. Most of the genes associated with germ layer specification are modified by H3K4me3 or co‐modified by H3K4me3 and H3K27me3. We named this new type of MSCs as adult multipotent adipose‐derived stem cells (M‐ADSCs). Using a four‐step nonviral system, M‐ADSCs can be efficiently Induced into hepatocyte like cells with expression of hepatocyte markers, drug metabolizing enzymes and transporters, and the other basic functional properties including albumin (ALB) secretion, glycogen storage, detoxification, low‐density lipoprotein intake, and lipids accumulation. In vivo both M‐ADSCs‐derived hepatoblasts and hepatocytes could form vascularized liver‐like tissue, secrete ALB and express metabolic enzymes. Single‐cell RNA‐seq was used to investigate the important stages in this conversion. M‐ADSCs could be converted to a functionally multipotent state during the preinduction stage without undergoing reprogramming process. Our findings provide important insights into mechanisms underlying cell development and conversion. stem cells translational medicine 2018;7:792–805
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影响因子：
46.9
作者：
通讯作者：
--
影响因子：
11.8
作者：
Chung, Won-Suk;Shin, Chong Hyun;Stainier, Didier Y. R.
通讯作者：
Stainier, Didier Y. R.
影响因子：
46.9
作者：
Ji, Hongkai;Jiang, Hui;Ma, Wenxiu;Johnson, David S.;Myers, Richard M.;Wong, Wing H.
通讯作者：
Wong, Wing H.
影响因子：
56.9
作者：
Matsumoto, K;Yoshitomi, H;Zaret, KS
通讯作者：
Zaret, KS
影响因子：
23.9
作者：
Du, Yuanyuan;Wang, Jinlin;Deng, Hongkui
通讯作者：
Deng, Hongkui