Refinement of the four-dimensional human heart atlas during the first trimester of gestation with rare and diverse cell states

Abstract

Samina Kausar1,*, Marine Herbane1,*, Elise Marechal1, Fabienne Lescroart1, Nicolas Lenfant1, Céline Chevalier1, Mathias Moreno1, Yorick Gitton2, Séverine Mazaud-Guittot3, Paolo Giacobini4, Alain Chédotal2, Anaïs Baudot1, Stéphane Zaffran1,, Heather C. Etchevers1,1 Aix Marseille Univ, INSERM, MMG, Marseille, France2 INSERM, CNRS, Institut de la Vision, Sorbonne Université, Paris, France3 Inserm, EHESP, Irset (Institut de recherche en santé, environnement et travail), UMR_S 1085, Université Rennes, Rennes, France4 Laboratory of Development and Plasticity of the Neuroendocrine Brain, Inserm, CHU Lille, Lille Neuroscience and Cognition, UMR-S 1172, Université Lille, Lille, France* These authors contributed equally to this work and are joint first authors These authors share joint last authorship; correspondence may be addressed to both ([email protected], [email protected]).International audienceCongenital heart defects represent a significant, frequent health burden. Understanding their developmental origins promises improved diagnoses, prognoses and therapies. The French Human Developmental Cell Atlas (HuDeCA) consortium refines the cell identity atlas in human hearts from 8 to 12 post-conceptional weeks using single-nucleus/spatial transcriptomics and advanced imaging approaches. We integrate and validate both across our datasets and with existing atlases, using multiple technical approaches to establish varying levels of resolution. The gene expression networks deployed within individual cells at specific positions reveal semi-continuous identities, reflecting positional paracrine influences exerted by/on the many lineages of the first and longest-lived vital organ