Deconstructing stem cell population heterogeneity: single-cell analysis and modeling approaches.
Deconstructing stem cell population heterogeneity: single-cell analysis and modeling approaches.
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DOI：
10.1016/j.biotechadv.2013.09.001
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发表时间：
2013-11-15
影响因子：
16
通讯作者：
Tzanakakis, Emmanuel S.
中科院分区：
文献类型：
--
作者：
Wu, Jincheng;Tzanakakis, Emmanuel S.
关键词：
同基因干细胞群体在许多属性中显示细胞间变异，包括基因或蛋白质表达、表观遗传状态、形态、增殖和分化倾向。所观察到的异质性的起源及其在维持多能性和干细胞谱系特化中的作用仍不清楚。解决相关问题将需要采用单细胞分析方法，因为传统的细胞生物化学和生物分子测定主要产生群体平均数据。除了延时显微镜和流式细胞术，单细胞基因组，转录组和蛋白质组分析的最新进展进行了审查。多重置换扩增、下一代测序、质谱仪和光谱法在干细胞系统中的应用有望提供丰富的信息，从而在促进多能性或定型的限定条件下提供前所未有水平的细胞系综的多参数表征。建立单细胞分析信息和观察到的表型之间的联系也需要合适的数学模型。干细胞的自我更新和分化是通过跨多个时间尺度的亚细胞、细胞间和生态位过程的协调调节来协调的。在这里，我们讨论了不同的建模方法和挑战，从他们的应用到干细胞群体。将单细胞分析与计算方法相结合将填补我们对干细胞生理学异质性功能的认识空白。这种组合还将有助于合理设计有效的分化和重编程策略以及用于生产具有临床价值的干细胞衍生物的生物过程。
Isogenic stem cell populations display cell-to-cell variations in a multitude of attributes including gene or protein expression, epigenetic state, morphology, proliferation and proclivity for differentiation. The origins of the observed heterogeneity and its roles in the maintenance of pluripotency and the lineage specification of stem cells remain unclear. Addressing pertinent questions will require the employment of single-cell analysis methods as traditional cell biochemical and biomolecular assays yield mostly population-average data. In addition to time-lapse microscopy and flow cytometry, recent advances in single-cell genomic, transcriptomic and proteomic profiling are reviewed. The application of multiple displacement amplification, next generation sequencing, mass cytometry and spectrometry to stem cell systems is expected to provide a wealth of information affording unprecedented levels of multiparametric characterization of cell ensembles under defined conditions promoting pluripotency or commitment. Establishing connections between single-cell analysis information and the observed phenotypes will also require suitable mathematical models. Stem cell self-renewal and differentiation are orchestrated by the coordinated regulation of subcellular, intercellular and niche-wide processes spanning multiple time scales. Here, we discuss different modeling approaches and challenges arising from their application to stem cell populations. Integrating single-cell analysis with computational methods will fill gaps in our knowledge about the functions of heterogeneity in stem cell physiology. This combination will also aid the rational design of efficient differentiation and reprogramming strategies as well as bioprocesses for the production of clinically valuable stem cell derivatives.
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影响因子：
16.8
作者：
Bendall SC;Nolan GP;Roederer M;Chattopadhyay PK
通讯作者：
Chattopadhyay PK
影响因子：
12.3
作者：
Carpenter AE;Jones TR;Lamprecht MR;Clarke C;Kang IH;Friman O;Guertin DA;Chang JH;Lindquist RA;Moffat J;Golland P;Sabatini DM
通讯作者：
Sabatini DM
DOI：
10.1126/science.1198704
发表时间：
2011-05-06
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Bendall SC;Simonds EF;Qiu P;Amir el-AD;Krutzik PO;Finck R;Bruggner RV;Melamed R;Trejo A;Ornatsky OI;Balderas RS;Plevritis SK;Sachs K;Pe'er D;Tanner SD;Nolan GP
通讯作者：
Nolan GP
影响因子：
64.8
作者：
Chang, Hannah H.;Hemberg, Martin;Huang, Sui
通讯作者：
Huang, Sui
影响因子：
4.3
作者：
Baserga, Renato
通讯作者：
Baserga, Renato