Liu Lin L, Brumbaugh Justin, Bar-Nur Ori, Smith Zachary, Stadtfeld Matthias, Meissner Alexander, Hochedlinger Konrad, Michor Franziska
Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, MA 02115, USA; Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA.
Massachusetts General Hospital Cancer Center and Center for Regenerative Medicine, Boston, MA 02114, USA; Harvard Stem Cell Institute, Cambridge, MA 02138, USA; Department of Stem Cell and Regenerative Biology, Cambridge, MA 02138, USA.
Cell Rep. 2016 Dec 20;17(12):3395-3406. doi: 10.1016/j.celrep.2016.11.080.
Reprogramming of somatic cells to induced pluripotent stem cells (iPSCs) is typically an inefficient and asynchronous process. A variety of technological efforts have been made to accelerate and/or synchronize this process. To define a unified framework to study and compare the dynamics of reprogramming under different conditions, we developed an in silico analysis platform based on mathematical modeling. Our approach takes into account the variability in experimental results stemming from probabilistic growth and death of cells and potentially heterogeneous reprogramming rates. We suggest that reprogramming driven by the Yamanaka factors alone is a more heterogeneous process, possibly due to cell-specific reprogramming rates, which could be homogenized by the addition of additional factors. We validated our approach using publicly available reprogramming datasets, including data on early reprogramming dynamics as well as cell count data, and thus we demonstrated the general utility and predictive power of our methodology for investigating reprogramming and other cell fate change systems.
将体细胞重编程为诱导多能干细胞（iPSC）通常是一个低效且不同步的过程。人们已经做出了各种技术努力来加速和/或同步这一过程。为了定义一个统一的框架来研究和比较不同条件下重编程的动态过程，我们基于数学建模开发了一个计算机模拟分析平台。我们的方法考虑了由于细胞的概率性生长和死亡以及潜在的异质重编程速率而导致的实验结果的变异性。我们认为仅由山中因子驱动的重编程是一个更加异质的过程，这可能是由于细胞特异性的重编程速率所致，而添加其他因子可能会使其同质化。我们使用公开可用的重编程数据集验证了我们的方法，这些数据集包括早期重编程动态数据以及细胞计数数据，因此我们证明了我们的方法在研究重编程和其他细胞命运改变系统方面的通用性和预测能力。
