Tools4Cells: Machine-learning aided morphodynamics characterization of stem cell differentiation using label-free microscopies

胚胎可以发育成由不同类型的细胞组成的有机体，不同类型的细胞在一定条件下可以相互转换，这是大自然的一个巨大奇迹。机械地理解和操纵不同细胞类型之间的转换是一个令人兴奋的研究前沿。这一研究领域有可能有助于我们理解发育以及组织和器官再生方面的创新。这个项目的目标是开发用于分析细胞电影的计算工具，以了解单个细胞如何从一种类型转变为另一种类型。这类似于跟踪人们从一个城市开车到另一个城市的路线，这样人们就可以识别主要路线，并尝试将交通引导到特定路线。这项工作的更广泛影响包括研究的内在价值，因为该平台可能被证明对其他一些项目有用。研究机会将提供给本科生和研究生以及博士后研究人员。外展工作将包括利用YouTube向公众推广科学。不同表型的细胞具有不同的形态和基因表达模式。当受到特定刺激和微环境时，它们可以在不同的表型之间转换，重新编程成为诱导的多能干细胞。然而，对这种细胞表型转变(CPT)过程的机械性理解遇到了快照数据不能提供时间信息的挑战。活细胞成像为连续监测单个细胞随时间的变化提供了另一种方法。该项目旨在开发一个普遍适用的平台和相关的计算机包，以(1)允许典型的细胞生物学实验室应用该平台并研究细胞过程，而不需要具有机器学习、图像分析或动力学系统理论的强大背景；(2)扩展到各种成像平台和模式，特别是与机器学习方法一起流行的基于定量相位成像的无标记成像。除了传统的生物图像信息学方法之外，这里的新奇之处在于在动力系统理论/系统生物学的框架下对CPT动力学的机制研究。此外，受图像数据库ImageNet在最近人工智能发展中发挥的关键作用的启发，研究人员将提供该项目生成的带注释的细胞图像，作为社区开发和测试图像分析方法的基准。开发的框架将普遍适用于研究大量的细胞表型转换过程。这一奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

It is a great wonder of Nature that an embryo can develop into an organism composed with different types of cells, and different types of cells can interconvert under certain conditions. Mechanistic understanding and manipulation of conversion between different cell types emerge as an exciting frontier of research. This area of research has the potential to contribute to our understanding of development as well as to innovations in tissue and organ regeneration. The goal of this project is to develop computational tools for analyzing movies of cells to learn how individual cells change from one type to another one. It is analogous to tracing the routes people take for driving from one city to another one, so one can identify the dominant routes and try to direct traffic to specific route. The Broader Impacts of the work include the intrinsic merit of the research as the platform could prove useful to a number of other projects. Research opportunities will be made available to undergraduate and graduate students along with post-doctoral researchers. Outreach effort will involve the use of YouTube to promote science to the general public.Cells of different phenotypes are characterized by distinct morphology and gene expression patterns. When subject to specific stimuli and microenvironments they can transit between distinct phenotypes, reprogramming to become induced pluripotent stem cells. Mechanistic understanding of such cell phenotypic transition (CPT) processes, however, suffers from the challenge that snapshot data cannot provide temporal information. Live-cell imaging provides an alternative approach for monitoring transitions of individual cells continuously over time. The project aims to develop a generally applicable platform and associated computer package that (1) allows typical cell biology labs to apply the platform and study cellular processes without requirements of a strong background in machine-learning, image analyses, or dynamical systems theories; (2) extends to various imaging platforms and modalities, especially quantitative phase imaging-based label-free imaging that has gained popularity together with machine-learning approaches. Beyond the traditional bioimage informatics approaches, the novelty here is for mechanistic studies of CPT dynamics in the framework of dynamical systems theory/systems biology. In addition, inspired by the critical role the image database ImageNet has played on the recent advance of artificial intelligence development, the researchers will provide annotated cell images generated from this project as benchmarks for the community to develop and test image analysis approaches. The developed framework will be generally applicable to study a large number of cell phenotype conversion processes.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.