Developmental role of macrophages modeled in human pluripotent stem cell-derived intestinal tissue
Andrew T. Song,
Renata H.M. Sindeaux,
Yuanyi Li,
Hicham Affia,
Tapan Agnihotri,
Severine Leclerc,
Patrick Piet van Vliet,
Mathieu Colas,
Jean-Victor Guimond,
Natalie Patey,
Lara Feulner,
Jean-Sebastien Joyal,
Elie Haddad,
Luis Barreiro,
Gregor Andelfinger
Affiliations
Andrew T. Song
Centre de Recherche, CHU Sainte-Justine, Montréal, QC, Canada; Department of Anatomy and Cell Biology, McGill University, Montréal, QC, Canada; Corresponding author
Renata H.M. Sindeaux
Centre de Recherche, CHU Sainte-Justine, Montréal, QC, Canada; Meakins Christie Laboratories, Department of Medicine, Department of Microbiology and Immunology, Department of Pathology Research Institute of McGill University Health Centre, Montréal, QC, Canada
Yuanyi Li
Centre de Recherche, CHU Sainte-Justine, Montréal, QC, Canada
Hicham Affia
Centre de Recherche, CHU Sainte-Justine, Montréal, QC, Canada
Tapan Agnihotri
Centre de Recherche, CHU Sainte-Justine, Montréal, QC, Canada; Department of Pharmacology and Therapeutics, McGill University, Montréal, QC, Canada
Severine Leclerc
Centre de Recherche, CHU Sainte-Justine, Montréal, QC, Canada
Patrick Piet van Vliet
Centre de Recherche, CHU Sainte-Justine, Montréal, QC, Canada
Mathieu Colas
Centre de Recherche, CHU Sainte-Justine, Montréal, QC, Canada
Jean-Victor Guimond
CLSC des Faubourgs, CIUSSS du Centre-Sud-de-l’Ile-de-Montréal, Montréal, QC, Canada
Natalie Patey
Department of Pathology, CHU Sainte-Justine, Université de Montréal, Montréal, QC, Canada
Lara Feulner
Centre de Recherche, CHU Sainte-Justine, Montréal, QC, Canada
Jean-Sebastien Joyal
Centre de Recherche, CHU Sainte-Justine, Montréal, QC, Canada; Département de Pédiatrie, Université de Montréal, Montréal, QC, Canada; Department of Pharmacology and Therapeutics, McGill University, Montréal, QC, Canada
Elie Haddad
Centre de Recherche, CHU Sainte-Justine, Montréal, QC, Canada; Département de Pédiatrie, Université de Montréal, Montréal, QC, Canada
Luis Barreiro
Centre de Recherche, CHU Sainte-Justine, Montréal, QC, Canada; Genetics Genomics and Systems Biology, University of Chicago, Chicago, IL, USA
Gregor Andelfinger
Centre de Recherche, CHU Sainte-Justine, Montréal, QC, Canada; Department of Anatomy and Cell Biology, McGill University, Montréal, QC, Canada; Département de Pédiatrie, Université de Montréal, Montréal, QC, Canada; Corresponding author
Summary: Macrophages populate the embryo early in gestation, but their role in development is not well defined. In particular, specification and function of macrophages in intestinal development remain little explored. To study this event in the human developmental context, we derived and combined human intestinal organoid and macrophages from pluripotent stem cells. Macrophages migrate into the organoid, proliferate, and occupy the emerging microanatomical niches of epithelial crypts and ganglia. They also acquire a transcriptomic profile similar to that of fetal intestinal macrophages and display tissue macrophage behaviors, such as recruitment to tissue injury. Using this model, we show that macrophages reduce glycolysis in mesenchymal cells and limit tissue growth without affecting tissue architecture, in contrast to the pro-growth effect of enteric neurons. In short, we engineered an intestinal tissue model populated with macrophages, and we suggest that resident macrophages contribute to the regulation of metabolism and growth of the developing intestine.
