Machine learning-based classification of dual fluorescence signals reveals muscle stem cell fate transitions in response to regenerative niche factors

The proper regulation of muscle stem cell (MuSC) fate by cues from the niche is essential for regeneration of skeletal muscle. How pro-regenerative niche factors control the dynamics of MuSC fate decisions remains unknown due to limitations of population-level endpoint assays. To address this knowle...

Full description

Saved in:
Bibliographic Details
Published in:npj Regenerative medicine 2023-01, Vol.8 (1), p.4-4, Article 4
Main Authors: Togninalli, Matteo, Ho, Andrew T. V., Madl, Christopher M., Holbrook, Colin A., Wang, Yu Xin, Magnusson, Klas E. G., Kirillova, Anna, Chang, Andrew, Blau, Helen M.
Format: Article
Language:English
Subjects:
631/532/2139
631/532/2439
631/61/54/2295
Biomaterials
Biomedical and Life Sciences
Biomedicine
Cell Biology
Immunology
Machine learning
Regenerative Medicine/Tissue Engineering
Stem Cells
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:The proper regulation of muscle stem cell (MuSC) fate by cues from the niche is essential for regeneration of skeletal muscle. How pro-regenerative niche factors control the dynamics of MuSC fate decisions remains unknown due to limitations of population-level endpoint assays. To address this knowledge gap, we developed a dual fluorescence imaging time lapse (Dual-FLIT) microscopy approach that leverages machine learning classification strategies to track single cell fate decisions with high temporal resolution. Using two fluorescent reporters that read out maintenance of stemness and myogenic commitment, we constructed detailed lineage trees for individual MuSCs and their progeny, classifying each division event as symmetric self-renewing, asymmetric, or symmetric committed. Our analysis reveals that treatment with the lipid metabolite, prostaglandin E2 (PGE2), accelerates the rate of MuSC proliferation over time, while biasing division events toward symmetric self-renewal. In contrast, the IL6 family member, Oncostatin M (OSM), decreases the proliferation rate after the first generation, while blocking myogenic commitment. These insights into the dynamics of MuSC regulation by niche cues were uniquely enabled by our Dual-FLIT approach. We anticipate that similar binary live cell readouts derived from Dual-FLIT will markedly expand our understanding of how niche factors control tissue regeneration in real time.
ISSN:2057-3995
2057-3995
DOI:10.1038/s41536-023-00277-4