Quantitative phase imaging with temporal kinetics predicts hematopoietic stem cell diversity

Takao Yogo (), Yuichiro Iwamoto, Hans Jiro Becker, Takaharu Kimura, Reiko Ishida, Ayano Sugiyama-Finnis, Tomomasa Yokomizo, Toshio Suda, Sadao Ota and Satoshi Yamazaki ()
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Takao Yogo: The University of Tokyo
Yuichiro Iwamoto: The University of Tokyo
Hans Jiro Becker: The University of Tokyo
Takaharu Kimura: The University of Tokyo
Reiko Ishida: The University of Tokyo
Ayano Sugiyama-Finnis: The University of Tokyo
Tomomasa Yokomizo: Tokyo Women’s Medical University
Toshio Suda: Kumamoto University
Sadao Ota: The University of Tokyo
Satoshi Yamazaki: The University of Tokyo

Nature Communications, 2025, vol. 16, issue 1, 1-14

Abstract: 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.

Date: 2025
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DOI: 10.1038/s41467-025-61846-3

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