Deep learning-enhanced morphological profiling predicts cell fate dynamics in real-time in hPSCs
SUMMARY Predicting how stem cells become patterned and differentiated into target tissues is key for optimising human tissue design. Here, we established DEEP-MAP - for deep learning-enhanced morphological profiling - an approach that integrates single-cell, multi-day, multi-colour microscopy phenomics with deep learning and allows to robustly map and predict cell fate dynamics in real-time without a need for cell state-specific reporters. Using human pluripotent stem cells (hPSCs) engineered to co-express the histone H2B and two-colour FUCCI cell cycle reporters, we used DEEP-MAP to capture hundreds of morphological- and proliferation-associated features for hundreds of thousands of cells and used this information to map and predict spatiotemporally single-cell fate dynamics across germ layer cell fates. We show that DEEP-MAP predicts fate changes as early or earlier than transcription factor-based fate reporters, reveals the timing and existence of intermediate cell fates invisible to fixed-cell technologies, and identifies proliferative properties predictive of cell fate transitions. DEEP-MAP provides a versatile, universal strategy to map tissue evolution and organisation across many developmental and tissue engineering contexts..
Medienart: |
Preprint |
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Erscheinungsjahr: |
2023 |
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Erschienen: |
2023 |
Enthalten in: |
bioRxiv.org - (2023) vom: 06. Nov. Zur Gesamtaufnahme - year:2023 |
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Sprache: |
Englisch |
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Beteiligte Personen: |
Ren, Edward [VerfasserIn] |
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Links: |
Volltext [kostenfrei] |
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Themen: |
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doi: |
10.1101/2021.07.31.454574 |
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funding: |
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Förderinstitution / Projekttitel: |
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PPN (Katalog-ID): |
XBI032309260 |
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520 | |a SUMMARY Predicting how stem cells become patterned and differentiated into target tissues is key for optimising human tissue design. Here, we established DEEP-MAP - for deep learning-enhanced morphological profiling - an approach that integrates single-cell, multi-day, multi-colour microscopy phenomics with deep learning and allows to robustly map and predict cell fate dynamics in real-time without a need for cell state-specific reporters. Using human pluripotent stem cells (hPSCs) engineered to co-express the histone H2B and two-colour FUCCI cell cycle reporters, we used DEEP-MAP to capture hundreds of morphological- and proliferation-associated features for hundreds of thousands of cells and used this information to map and predict spatiotemporally single-cell fate dynamics across germ layer cell fates. We show that DEEP-MAP predicts fate changes as early or earlier than transcription factor-based fate reporters, reveals the timing and existence of intermediate cell fates invisible to fixed-cell technologies, and identifies proliferative properties predictive of cell fate transitions. DEEP-MAP provides a versatile, universal strategy to map tissue evolution and organisation across many developmental and tissue engineering contexts. | ||
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700 | 1 | |a Kim, Sungmin |4 aut | |
700 | 1 | |a Mohamad, Saad |4 aut | |
700 | 1 | |a Huguet, Samuel F. |4 aut | |
700 | 1 | |a Shi, Yulin |4 aut | |
700 | 1 | |a Cohen, Andrew R. |4 aut | |
700 | 1 | |a Piddini, Eugenia |0 (orcid)0000-0003-3901-076X |4 aut | |
700 | 1 | |a Salas, Rafael Carazo |0 (orcid)0000-0002-5943-3981 |4 aut | |
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