Prenatal inflammation perturbs murine fetal hematopoietic development and 
causes persistent changes to postnatal immunity

López, Diego A; Apostol, April C; Lebish, Eric J; Valencia, Clint H; Romero-Mulero, Mari Carmen; Pavlovich, Polina V; Hernandez, Gloria E; Forsberg, E Camilla; Cabezas-Wallscheid, Nina; Beaudin, Anna E

doi:10.1016/j.celrep.2022.111677

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Prenatal inflammation perturbs murine fetal hematopoietic development and causes persistent changes to postnatal immunity

MPS-Authors

Romero-Mulero, Mari Carmen
Department of Cellular and Molecular Immunology, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

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Cabezas-Wallscheid, Nina
Department of Cellular and Molecular Immunology, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

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Citation

López, D. A., Apostol, A. C., Lebish, E. J., Valencia, C. H., Romero-Mulero, M. C., Pavlovich, P. V., et al. (2022). Prenatal inflammation perturbs murine fetal hematopoietic development and causes persistent changes to postnatal immunity. Cell Reports, 41: 111677. doi:10.1016/j.celrep.2022.111677.

Cite as: https://hdl.handle.net/21.11116/0000-000D-15E5-9

Abstract

Adult hematopoietic stem and progenitor cells (HSPCs) respond directly to inflammation and infection, causing both acute and persistent changes to quiescence, mobilization, and differentiation. Here we show that murine fetal HSPCs respond to prenatal inflammation in utero and that the fetal response shapes postnatal hematopoiesis and immune cell function. Heterogeneous fetal HSPCs show divergent responses to maternal immune activation (MIA), including changes in quiescence, expansion, and lineage-biased output. Single-cell transcriptomic analysis of fetal HSPCs in response to MIA reveals specific upregulation of inflammatory gene profiles in discrete, transient hematopoietic stem cell (HSC) populations that propagate expansion of lymphoid-biased progenitors. Beyond fetal development, MIA causes the inappropriate expansion and persistence of fetal lymphoid-biased progenitors postnatally, concomitant with increased cellularity and hyperresponsiveness of fetal-derived innate-like lymphocytes. Our investigation demonstrates how inflammation in utero can direct the output and function of fetal-derived immune cells by reshaping fetal HSC establishment.