Virtual cells in a virtual microenvironment recapitulate early development-like patterns in human pluripotent stem cell colonies.
Virtual cells in a virtual microenvironment recapitulate early development-like patterns in human pluripotent stem cell colonies.
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DOI：
10.1016/j.stemcr.2022.10.004
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发表时间：
2023-01-10
影响因子：
5.9
通讯作者：
Zandstra, Peter W.
中科院分区：
文献类型：
--
作者：
Kaul, Himanshu;Werschler, Nicolas;Jones, Ross D.;Siu, M. Mona;Tewary, Mukul;Hagner, Andrew;Ostblom, Joel;Aguilar-Hidalgo, Daniel;Zandstra, Peter W.
形态发生信号参与早期胚胎组织模式化调控网络的机制还不完全清楚。在这里，我们开发了一个最小的基因调控网络（GRN）模型的人多能干细胞（hPSC）谱系承诺，并将其嵌入到“细胞”代理，响应于一个动态的形态发生信号微环境。模拟表明，GRN布线有显着的非直观的影响，组织图案的顺序，组成和动力学。GRN连接的实验扰动支持模型预测，并证明了OCT 4作为原肠胚周围命运的主调节器的作用。我们所谓的加尔门策略提供了一个多尺度计算平台，以了解基于单细胞的调控相互作用如何扩展到组织域。这个基础提供了新的机会来模拟网络基序对正常和异常组织发育的影响。一个最小的多能性GRN捕获微模式中的胚层出现一个主GRN可以产生不同的组织，基于细胞间/细胞内背景细胞解码位置，通过考虑梯度累积OCT 4作为一个主调节器，用于成熟的hPSC中的胚层标记在这里，Kaul和同事报告了一个计算框架，通过耦合GRN活性与动态信号通过代理。他们表明，根据信号背景，主GRN可以导致不同的组织。他们展示了GRNs如何协调活动，以产生可以预测控制的发展波。一个关键的发现是细胞通过累积考虑梯度来解码位置。
The mechanism by which morphogenetic signals engage the regulatory networks responsible for early embryonic tissue patterning is incompletely understood. Here, we developed a minimal gene regulatory network (GRN) model of human pluripotent stem cell (hPSC) lineage commitment and embedded it into “cellular” agents that respond to a dynamic morphogenetic signaling microenvironment. Simulations demonstrated that GRN wiring had significant non-intuitive effects on tissue pattern order, composition, and dynamics. Experimental perturbation of GRN connectivities supported model predictions and demonstrated the role of OCT4 as a master regulator of peri-gastrulation fates. Our so-called GARMEN strategy provides a multiscale computational platform to understand how single-cell-based regulatory interactions scale to tissue domains. This foundation provides new opportunities to simulate the impact of network motifs on normal and aberrant tissue development. A minimal pluripotency GRN captures germ-layer emergence in micropatterns A master GRN can yield different tissues based on the inter-/intracellular context Cells decode position by considering gradients cumulatively OCT4 acts as a master regulator for the maturation of germ-layer markers in hPSCs Here, Kaul and colleagues report on a computational framework by coupling GRN activity with dynamic signaling via agents. They show that a master GRN can lead to different tissues depending on the signaling context. They demonstrate how GRNs orchestrate activity to yield developmental waves that can be predictively controlled. A key finding is that cells decode position by considering gradients cumulatively.
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影响因子：
4.3
作者：
Heydari T;A Langley M;Fisher CL;Aguilar-Hidalgo D;Shukla S;Yachie-Kinoshita A;Hughes M;M McNagny K;Zandstra PW
通讯作者：
Zandstra PW
影响因子：
9.8
作者：
McQuin C;Goodman A;Chernyshev V;Kamentsky L;Cimini BA;Karhohs KW;Doan M;Ding L;Rafelski SM;Thirstrup D;Wiegraebe W;Singh S;Becker T;Caicedo JC;Carpenter AE
通讯作者：
Carpenter AE
影响因子：
16.6
作者：
Jones RD;Qian Y;Siciliano V;DiAndreth B;Huh J;Weiss R;Del Vecchio D
通讯作者：
Del Vecchio D
DOI：
10.1073/pnas.1406482111
发表时间：
2014-11-04
影响因子：
11.1
作者：
Hansen, Jonathan;Mailand, Erik;Benenson, Yaakov
通讯作者：
Benenson, Yaakov
影响因子：
9.8
作者：
Chhabra, Sapna;Liu, Lizhong;Warmflash, Aryeh
通讯作者：
Warmflash, Aryeh