Developmental role of macrophages modeled in human pluripotent stem cell-derived intestinal tissue

Song, Andrew T.; Sindeaux, Renata H. M.; Li, Yuanyi; Affia, Hicham; Agnihotri, Tapan; Leclerc, Severine; van Vliet, Patrick Piet; Colas, Mathieu; Guimond, Jean-Victor; Patey, Natalie; Feulner, Lara; Joyal, Jean-Sebastien; Haddad, Elie; Barreiro, Luis; Andelfinger, Gregor

doi:10.6082/w6sc8-a1z52

Published December 26, 2023 | Version v1

Journal article Open

Developmental role of macrophages modeled in human pluripotent stem cell-derived intestinal tissue

1. CHU Sainte-Justine
2. CIUSSS du Centre-Sud-de-l'Ile-de-Montréal
3. University of Chicago

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.

Data availability

Single-cell RNA-seq data have been deposited at SRA and are publicly available as of the date of publication. Accession number NCBI: PRJNA890190.

This paper does not report original code. Refer to STAR Methods details for single-cell RNA-seq analyses pipeline.

Any additional information in this paper, including the microscopy data, required to reanalyze the data reported here is available from the lead contact upon request.

Files