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深度神经网络追踪人类多能干细胞揭示了指导形态发生的内在行为。

Deep neural net tracking of human pluripotent stem cells reveals intrinsic behaviors directing morphogenesis.

机构信息

UC Berkeley-UC San Francisco Graduate Program in Bioengineering, San Francisco, CA, USA; Gladstone Institutes, San Francisco, CA, USA.

Gladstone Institutes, San Francisco, CA, USA; Developmental and Stem Cell Biology PhD Program, University of California, San Francisco, San Francisco, CA, USA.

出版信息

Stem Cell Reports. 2021 May 11;16(5):1317-1330. doi: 10.1016/j.stemcr.2021.04.008.

DOI:10.1016/j.stemcr.2021.04.008
PMID:33979602
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8185472/
Abstract

Lineage tracing is a powerful tool in developmental biology to interrogate the evolution of tissue formation, but the dense, three-dimensional nature of tissue limits the assembly of individual cell trajectories into complete reconstructions of development. Human induced pluripotent stem cells (hiPSCs) can recapitulate aspects of developmental processes, providing an in vitro platform to assess the dynamic collective behaviors directing tissue morphogenesis. Here, we trained an ensemble of neural networks to track individual hiPSCs in time-lapse microscopy, generating longitudinal measures of cell and cellular neighborhood properties on timescales from minutes to days. Our analysis reveals that, while individual cell parameters are not strongly affected by pluripotency maintenance conditions or morphogenic cues, regional changes in cell behavior predict cell fate and colony organization. By generating complete multicellular reconstructions of hiPSC behavior, our tracking pipeline enables fine-grained understanding of morphogenesis by elucidating the role of regional behavior in early tissue formation.

摘要

谱系追踪是发育生物学中的一种强大工具，可用于研究组织形成的演化，但组织的密集三维性质限制了将单个细胞轨迹组装成完整的发育重建。人类诱导多能干细胞（hiPSC）可以再现发育过程的某些方面，为评估指导组织形态发生的动态集体行为提供了体外平台。在这里，我们训练了一个神经网络集合来对延时显微镜中的单个 hiPSC 进行跟踪，从而在从分钟到几天的时间尺度上生成细胞和细胞邻域特性的纵向测量值。我们的分析表明，尽管单个细胞参数不受多能性维持条件或形态发生线索的强烈影响，但细胞行为的区域变化可预测细胞命运和集落组织。通过生成 hiPSC 行为的完整多细胞重建，我们的跟踪管道通过阐明区域行为在早期组织形成中的作用，实现了对形态发生的精细理解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9be4/8185472/1d0e8ea2a5ba/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9be4/8185472/6daca0e53048/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9be4/8185472/34e53eab33f5/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9be4/8185472/18ef2eb507aa/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9be4/8185472/6ce8f154775f/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9be4/8185472/1d0e8ea2a5ba/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9be4/8185472/6daca0e53048/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9be4/8185472/34e53eab33f5/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9be4/8185472/18ef2eb507aa/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9be4/8185472/6ce8f154775f/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9be4/8185472/1d0e8ea2a5ba/gr5.jpg

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