Characterization of cell-fate decision landscapes by estimating transcription factor dynamics.
Fiche publication
Date publication
juillet 2023
Journal
Cell reports methods
Auteurs
Membres identifiés du Cancéropôle Est :
Dr GRADWOHL Gérard, Dr SCHREIBER Valérie, Dr MOLINA Nacho
Tous les auteurs :
Jiménez S, Schreiber V, Mercier R, Gradwohl G, Molina N
Lien Pubmed
Résumé
Time-specific modulation of gene expression during differentiation by transcription factors promotes cell diversity. However, estimating their dynamic regulatory activity at the single-cell level and in a high-throughput manner remains challenging. We present FateCompass, an integrative approach that utilizes single-cell transcriptomics data to identify lineage-specific transcription factors throughout differentiation. By combining a probabilistic framework with RNA velocities or differentiation potential, we estimate transition probabilities, while a linear model of gene regulation is employed to compute transcription factor activities. Considering dynamic changes and correlations of expression and activities, FateCompass identifies lineage-specific regulators. Our validation using data and application to pancreatic endocrine cell differentiation datasets highlight both known and potentially novel lineage-specific regulators. Notably, we uncovered undescribed transcription factors of an enterochromaffin-like population during differentiation toward ß-like cells. FateCompass provides a valuable framework for hypothesis generation, advancing our understanding of the gene regulatory networks driving cell-fate decisions.
Mots clés
RNA velocity, cell-fate modeling, differentiation, endocrine cell, gene regulation
Référence
Cell Rep Methods. 2023 07 24;3(7):100512