Quantitative phase imaging with temporal kinetics predicts hematopoietic stem cell diversity.

Journal: Nature communications
Published Date:

Abstract

Innovative identification technologies for hematopoietic stem cells (HSCs) have expanded the scope of stem cell biology. Clinically, the functional quality of HSCs critically influences the safety and therapeutic efficacy of stem cell therapies. However, most analytical techniques capture only a single snapshot, disregarding the temporal context. A comprehensive understanding of the temporal heterogeneity of HSCs necessitates live-cell, real-time and non-invasive analysis. Here, we developed a prediction system for HSC diversity by integrating single-HSC ex vivo expansion technology with quantitative phase imaging (QPI)-driven machine learning. By analyzing the cellular kinetics of individual HSCs, we discovered previously undetectable diversity that snapshot analysis cannot resolve. The QPI-driven algorithm quantitatively evaluates stemness at the single-cell level and leverages temporal information to significantly improve prediction accuracy. This platform advances the field from snapshot-based identification of HSCs to dynamic, time-resolved prediction of their functional quality based on past cellular kinetics.

Authors

  • Takao Yogo
    Division of Cell Regulation, Center for Experimental Medicine and Systems Biology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan. takayogo0430@g.ecc.u-tokyo.ac.jp.
  • Yuichiro Iwamoto
    Research Center for Advanced Science and Technology, The University of Tokyo, Meguro 4-6-1, Shibuya, Tokyo, Japan.
  • Hans Jiro Becker
    Division of Cell Regulation, Center for Experimental Medicine and Systems Biology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
  • Takaharu Kimura
    Division of Cell Regulation, Center for Experimental Medicine and Systems Biology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
  • Reiko Ishida
    Division of Cell Regulation, Center for Experimental Medicine and Systems Biology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
  • Ayano Sugiyama-Finnis
    Division of Cell Regulation, Center for Experimental Medicine and Systems Biology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
  • Tomomasa Yokomizo
    Department of Microscopic and Developmental Anatomy, Tokyo Women's Medical University, Tokyo, Japan.
  • Toshio Suda
    Cancer Science Institute, National University of Singapore, 14 Medical Drive, MD6, Singapore 117599, Singapore.
  • Sadao Ota
    Research Center for Advanced Science and Technology, The University of Tokyo, 4-6-1 Komaba, Meguro-ku, Tokyo 153-8904, Japan.
  • Satoshi Yamazaki
    Division of Cell Regulation, Center for Experimental Medicine and Systems Biology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan. y-sato4@ims.u-tokyo.ac.jp.