A liver-specific gene expression panel predicts the differentiation status of in vitro hepatocyte models.
A liver-specific gene expression panel predicts the differentiation status of in vitro hepatocyte models.
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DOI：
10.1002/hep.29324
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发表时间：
2017-11
期刊：
影响因子：
--
通讯作者：
Cho HS
中科院分区：
文献类型：
--
作者：
Kim DS;Ryu JW;Son MY;Oh JH;Chung KS;Lee S;Lee JJ;Ahn JH;Min JS;Ahn J;Kang HM;Kim J;Jung CR;Kim NS;Cho HS
替代细胞来源，如三维类器官和诱导多能干细胞衍生细胞，可能为药物开发应用和临床移植提供潜在有效的方法。例如，越来越需要开发用于基于肝细胞的治疗的细胞来源，并且进行肝移植以治疗患有严重终末期肝病的患者。分化的肝细胞和三维类器官有望为组织模型和革命性的临床治疗提供新的细胞来源。然而，确认肝脏特异性谱系标志物的表达水平的常规实验方法不能提供关于肝脏和分化细胞来源之间的分化状态或相似程度的完整信息。因此，在这项研究中，为了克服与评估分化的肝细胞和类器官相关的几个问题，我们开发了一种肝脏特异性基因表达面板（LiGEP）算法，该算法将肝脏相似性程度表示为“百分比”。我们证明了使用LiGEP算法计算的百分比与小鼠体内肝组织的发育阶段相关，表明LiGEP可以正确预测发育阶段。此外，三维培养的HepaRG细胞和人多能干细胞衍生的肝细胞样细胞显示肝脏相似性评分分别为59.14%和32%，尽管检测到一般肝脏特异性标志物。结论：我们的研究描述了分化样本的定量和预测模型，特别是肝脏特异性细胞或类器官;该模型可以进一步扩展到各种组织特异性类器官;我们的LiGEP可以提供有关体外肝脏模型分化状态的有用信息和见解。（Hepatology 2017;66：1662-1674）。
Alternative cell sources, such as three‐dimensional organoids and induced pluripotent stem cell–derived cells, might provide a potentially effective approach for both drug development applications and clinical transplantation. For example, the development of cell sources for liver cell–based therapy has been increasingly needed, and liver transplantation is performed for the treatment for patients with severe end‐stage liver disease. Differentiated liver cells and three‐dimensional organoids are expected to provide new cell sources for tissue models and revolutionary clinical therapies. However, conventional experimental methods confirming the expression levels of liver‐specific lineage markers cannot provide complete information regarding the differentiation status or degree of similarity between liver and differentiated cell sources. Therefore, in this study, to overcome several issues associated with the assessment of differentiated liver cells and organoids, we developed a liver‐specific gene expression panel (LiGEP) algorithm that presents the degree of liver similarity as a “percentage.” We demonstrated that the percentage calculated using the LiGEP algorithm was correlated with the developmental stages of in vivo liver tissues in mice, suggesting that LiGEP can correctly predict developmental stages. Moreover, three‐dimensional cultured HepaRG cells and human pluripotent stem cell–derived hepatocyte‐like cells showed liver similarity scores of 59.14% and 32%, respectively, although general liver‐specific markers were detected. Conclusion: Our study describes a quantitative and predictive model for differentiated samples, particularly liver‐specific cells or organoids; and this model can be further expanded to various tissue‐specific organoids; our LiGEP can provide useful information and insights regarding the differentiation status of in vitro liver models. (Hepatology 2017;66:1662–1674).
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影响因子：
4.6
作者：
Kim HM;Kim JW;Choi Y;Chun HS;Im I;Han YM;Song CW;Yoon S;Park HJ
通讯作者：
Park HJ
影响因子：
3.4
作者：
Grimm, SW;Richtand, NM;Reele, SB
通讯作者：
Reele, SB
影响因子：
--
作者：
Lozano E;Herraez E;Briz O;Robledo VS;Hernandez-Iglesias J;Gonzalez-Hernandez A;Marin JJ
通讯作者：
Marin JJ
DOI：
10.1242/dev.114215
发表时间：
2015-06-15
期刊：
Development (Cambridge, England)
影响因子：
--
作者：
Gordillo M;Evans T;Gouon-Evans V
通讯作者：
Gouon-Evans V
影响因子：
46.9
作者：
Kroon, Evert;Martinson, Laura A.;Baetge, Emmanuel E.
通讯作者：
Baetge, Emmanuel E.