Predicting differentiation potential of human pluripotent stem cells:Possibilities and challenges  

作　　者：Li-Ping Liu Yun-Wen Zheng 

机构地区：[1]Institute of Regenerative Medicine,Affiliated Hospital of Jiangsu University,Jiangsu University,Zhenjiang 212001,Jiangsu Province,China [2]University of Tsukuba Faculty of Medicine,Tsukuba,Ibaraki 305-8575,Japan [3]Yokohama City University School of Medicine,Yokohama 236-0004,Japan

出　　处：《World Journal of Stem Cells》2019年第7期375-382,共8页世界干细胞杂志（英文版）（电子版）

基　　金：Supported by National Natural Science Foundation of China,No.81770621;Ministry of Education,Culture,Sports,Science,and Technology of Japan,KAKENHI,No.16K15604 and No.18H02866;Natural Science Foundation of Jiangsu Province,No.BK20180281

摘　　要：The capability of human pluripotent stem cell(hPSC)lines to propagate indefinitely and differentiate into derivatives of three embryonic germ layers makes these cells be powerful tools for basic scientific research and promising agents for translational medicine.However,variations in differentiation tendency and efficiency as well as pluripotency maintenance necessitate the selection of hPSC lines for the intended applications to save time and cost.To screen the qualified cell lines and exclude problematic cell lines,their pluripotency must be confirmed initially by traditional methods such as teratoma formation or by highthroughput gene expression profiling assay.Additionally,their differentiation potential,particularly the lineage-specific differentiation propensities of hPSC lines,should be predicted in an early stage.As a complement to the teratoma assay,RNA sequencing data provide a quantitative estimate of the differentiation ability of hPSCs in vivo.Moreover,multiple scorecards have been developed based on selected gene sets for predicting the differentiation potential into three germ layers or the desired cell type many days before terminal differentiation.For clinical application of hPSCs,the malignant potential of the cells must also be evaluated.A combination of histologic examination of teratoma with quantitation of gene expression data derived from teratoma tissue provides safety-related predictive information by detecting immature teratomas,malignancy marker expression,and other parameters.Although various prediction methods are available,distinct limitations remain such as the discordance of results between different assays and requirement of a long time and high labor and cost,restricting their wide applications in routine studies.Therefore,simpler and more rapid detection assays with high specificity and sensitivity that can be used to monitor the status of hPSCs at any time and fewer targeted markers that are more specific for a given desired cell type are urgently needed.The capability of human pluripotent stem cell(hPSC) lines to propagate indefinitely and differentiate into derivatives of three embryonic germ layers makes these cells be powerful tools for basic scientific research and promising agents for translational medicine. However, variations in differentiation tendency and efficiency as well as pluripotency maintenance necessitate the selection of hPSC lines for the intended applications to save time and cost. To screen the qualified cell lines and exclude problematic cell lines, their pluripotency must be confirmed initially by traditional methods such as teratoma formation or by highthroughput gene expression profiling assay. Additionally, their differentiation potential, particularly the lineage-specific differentiation propensities of hPSC lines, should be predicted in an early stage. As a complement to the teratoma assay, RNA sequencing data provide a quantitative estimate of the differentiation ability of hPSCs in vivo. Moreover, multiple scorecards have been developed based on selected gene sets for predicting the differentiation potential into three germ layers or the desired cell type many days before terminal differentiation.For clinical application of hPSCs, the malignant potential of the cells must also be evaluated. A combination of histologic examination of teratoma with quantitation of gene expression data derived from teratoma tissue provides safety-related predictive information by detecting immature teratomas, malignancy marker expression, and other parameters. Although various prediction methods are available, distinct limitations remain such as the discordance of results between different assays and requirement of a long time and high labor and cost,restricting their wide applications in routine studies. Therefore, simpler and more rapid detection assays with high specificity and sensitivity that can be used to monitor the status of hPSCs at any time and fewer targeted markers that are more specific for a given desired cell type are urgently needed.

关 键 词：Human PLURIPOTENT STEM CELLS Induced PLURIPOTENT STEM CELLS Embryonic STEM CELLS DIFFERENTIATION POTENTIAL Prediction Pluripotency Malignant POTENTIAL EMBRYOID bodies Lineage-specific DIFFERENTIATION Teratoma 

分 类 号：R[医药卫生]