Distinct Gene Expression and Epigenetic Signatures in Hepatocyte-like Cells Produced by Different Strategies from the Same Donor.
Distinct Gene Expression and Epigenetic Signatures in Hepatocyte-like Cells Produced by Different Strategies from the Same Donor.
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来自同一供体的不同策略产生的肝细胞样细胞中不同的基因表达和表观遗传特征
DOI：
10.1016/j.stemcr.2017.10.019
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发表时间：
2017-12-12
影响因子：
5.9
通讯作者：
Hui L
中科院分区：
文献类型：
--
作者：
Gao Y;Zhang X;Zhang L;Cen J;Ni X;Liao X;Yang C;Li Y;Chen X;Zhang Z;Shu Y;Cheng X;Hay DC;Lai D;Pan G;Wei G;Hui L
肝细胞样细胞（HLC）可以通过定向分化或转分化产生。采用两种策略，我们从相同的供体细胞系产生诱导多能干细胞（iPSC）-HLC和hiHep。这两种类型的HLCs在基因表达谱分析过程中彼此明显聚类。特别是，在II期药物代谢和脂质积累的基因表达中存在差异，这由iPSC-HLCs和hiHep中的H3 K27乙酰化状态所支持。虽然在体外实现了不同的表型，但两种类型的HLC在移植到Fah缺陷小鼠后表现出相似的表型。总之，可以使用两种策略从同一供体获得功能性HLCs。整体基因表达定义了这些群体之间的差异在体外。重要的是，两种HLC在体内移植后均显示出部分但显著改善的肝功能，证明了可塑性以及在培养皿中基于细胞的建模和未来基于细胞的治疗的潜力。比较来自同一供体的hiHep和iPSC-HLCs hiHep和iPSC-HLCs显示不同的表达模式和肝功能hiHep和iPSC-HLCs中的不同表达部分归因于H3 K27 ac两种HLCs在肝脏的体内微环境中进一步成熟在这篇文章中，Hui及其同事表明，hiHep和iPSC-从同一供体产生的HLC显示与其肝功能相关的不同基因表达模式。不同的H3 K27 ac修饰部分解释了两种类型的HLC之间的功能差异。重要的是，两种HLC在小鼠肝脏中重新增殖后均显示出肝脏基因表达的改善。
Hepatocyte-like cells (HLCs) can be generated through directed differentiation or transdifferentiation. Employing two strategies, we generated induced pluripotent stem cell (iPSC)-HLCs and hiHeps from the same donor cell line. Both types of HLCs clustered distinctly from each other during gene expression profiling. In particular, differences existed in gene expression for phase II drug metabolism and lipid accumulation, underpinned by H3K27 acetylation status in iPSC-HLCs and hiHeps. While distinct phenotypes were achieved in vitro, both types of HLCs demonstrated similar phenotypes following transplantation into Fah-deficient mice. In conclusion, functional HLCs can be obtained from the same donor using two strategies. Global gene expression defined the differences between those populations in vitro. Importantly, both HLCs displayed partial but markedly improved hepatic function following transplantation in vivo, demonstrating plasticity and the potential for cell-based modeling in the dish and cell-based therapy in the future. hiHeps and iPSC-HLCs from the same donor are compared hiHeps and iPSC-HLCs show distinct expression patterns and hepatic functions Different expressions in hiHeps and iPSC-HLCs are partially attributed to H3K27ac Both HLCs are further matured in the in vivo microenvironment of livers In this article, Hui and colleagues show that hiHeps and iPSC-HLCs generated from the same donor display different gene expression patterns that correlate with their hepatic functions. Distinct H3K27ac modifications partially explain the functional differences between the two types of HLCs. Importantly, both HLCs show improved hepatic gene expression after repopulation in murine livers.
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影响因子：
46.9
作者：
Azuma, Hisaya;Paulk, Nicole;Grompe, Markus
通讯作者：
Grompe, Markus
DOI：
10.1126/science.1247391
发表时间：
2014-08-22
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Fox IJ;Daley GQ;Goldman SA;Huard J;Kamp TJ;Trucco M
通讯作者：
Trucco M
影响因子：
6.1
作者：
Rashidi H;Alhaque S;Szkolnicka D;Flint O;Hay DC
通讯作者：
Hay DC
影响因子：
25.7
作者：
Godoy P;Schmidt-Heck W;Natarajan K;Lucendo-Villarin B;Szkolnicka D;Asplund A;Björquist P;Widera A;Stöber R;Campos G;Hammad S;Sachinidis A;Chaudhari U;Damm G;Weiss TS;Nüssler A;Synnergren J;Edlund K;Küppers-Munther B;Hay DC;Hengstler JG
通讯作者：
Hengstler JG
影响因子：
23.9
作者：
Du, Yuanyuan;Wang, Jinlin;Deng, Hongkui
通讯作者：
Deng, Hongkui