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

Erscheinungsjahr:

2023

Erschienen:

2023

Enthalten in:

bioRxiv.org - (2023) vom: 06. Nov. Zur Gesamtaufnahme - year:2023

Sprache:

Englisch

Beteiligte Personen:

Ren, Edward [VerfasserIn]
Kim, Sungmin [VerfasserIn]
Mohamad, Saad [VerfasserIn]
Huguet, Samuel F. [VerfasserIn]
Shi, Yulin [VerfasserIn]
Cohen, Andrew R. [VerfasserIn]
Piddini, Eugenia [VerfasserIn]
Salas, Rafael Carazo [VerfasserIn]

Links:

Volltext [kostenfrei]

Themen:

570
Biology

doi:

10.1101/2021.07.31.454574

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

XBI032309260