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基于深度学习的造血干细胞和多能祖细胞功能亚群的预测分类

Deep learning-based predictive classification of functional subpopulations of hematopoietic stem cells and multipotent progenitors.

作者信息

Wang Shen, Han Jianzhong, Huang Jingru, Islam Khayrul, Shi Yuheng, Zhou Yuyuan, Kim Dongwook, Zhou Jane, Lian Zhaorui, Liu Yaling, Huang Jian

机构信息

Lehigh University Department of Mechanical Engineering and Mechanics.

Coriell Institute for Medical Research.

出版信息

Res Sq. 2023 Nov 14:rs.3.rs-3332530. doi: 10.21203/rs.3.rs-3332530/v1.

Abstract

BACKGROUND

Hematopoietic stem cells (HSCs) and multipotent progenitors (MPPs) play a pivotal role in maintaining lifelong hematopoiesis. The distinction between stem cells and other progenitors, as well as the assessment of their functions, has long been a central focus in stem cell research. In recent years, deep learning has emerged as a powerful tool for cell image analysis and classification/prediction.

METHODS

In this study, we explored the feasibility of employing deep learning techniques to differentiate murine HSCs and MPPs based solely on their morphology, as observed through light microscopy (DIC) images.

RESULTS

After rigorous training and validation using extensive image datasets, we successfully developed a three-class classifier, referred to as the LSM model, capable of reliably distinguishing long-term HSCs (LT-HSCs), short-term HSCs (ST-HSCs), and MPPs. The LSM model extracts intrinsic morphological features unique to different cell types, irrespective of the methods used for cell identification and isolation, such as surface markers or intracellular GFP markers. Furthermore, employing the same deep learning framework, we created a two-class classifier that effectively discriminates between aged HSCs and young HSCs. This discovery is particularly significant as both cell types share identical surface markers yet serve distinct functions. This classifier holds the potential to offer a novel, rapid, and efficient means of assessing the functional states of HSCs, thus obviating the need for time-consuming transplantation experiments.

CONCLUSION

Our study represents the pioneering use of deep learning to differentiate HSCs and MPPs under steady-state conditions. With ongoing advancements in model algorithms and their integration into various imaging systems, deep learning stands poised to become an invaluable tool, significantly impacting stem cell research.

摘要

背景

造血干细胞(HSCs)和多能祖细胞(MPPs)在维持终身造血过程中发挥着关键作用。干细胞与其他祖细胞之间的区别以及对其功能的评估,长期以来一直是干细胞研究的核心焦点。近年来,深度学习已成为细胞图像分析和分类/预测的强大工具。

方法

在本研究中,我们探讨了仅基于光学显微镜(DIC)图像观察到的形态,利用深度学习技术区分小鼠造血干细胞和多能祖细胞的可行性。

结果

在使用大量图像数据集进行严格训练和验证后,我们成功开发了一种三类分类器,称为LSM模型,能够可靠地区分长期造血干细胞(LT-HSCs)、短期造血干细胞(ST-HSCs)和多能祖细胞。LSM模型提取不同细胞类型独特的内在形态特征,而不考虑用于细胞鉴定和分离的方法,如表面标志物或细胞内GFP标志物。此外,使用相同的深度学习框架,我们创建了一个两类分类器,能够有效区分老年造血干细胞和年轻造血干细胞。这一发现尤为重要,因为这两种细胞类型具有相同的表面标志物,但功能不同。该分类器有可能提供一种新颖、快速且高效的评估造血干细胞功能状态的方法,从而无需进行耗时的移植实验。

结论

我们的研究代表了在稳态条件下利用深度学习区分造血干细胞和多能祖细胞的开创性应用。随着模型算法的不断进步及其与各种成像系统的整合,深度学习有望成为一种宝贵的工具,对干细胞研究产生重大影响。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/24df/10680918/4f51e3204c85/nihpp-rs3332530v1-f0001.jpg

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