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bioRxiv · 10.1101/2022.05.08.491095

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

Apostol, A. C.·Lopez, D. A.·Lebish, E. J.·Valencia, C. H.·Romero-Mulero, M. C.·Pavlovich, P.·Hernandez, G. E.·Forsberg, E. C.·Cabezas-Wallscheid, N.·Beaudin, A. E.
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Abstract

Adult hematopoietic stem and progenitor cells (HSPCs) respond directly to inflammation and infection, resulting in both acute and persistent changes to quiescence, mobilization, and differentiation. Here we show that fetal HSPCs respond to prenatal inflammation in utero, and that the fetal response shapes postnatal hematopoiesis and immunity. Heterogenous fetal HSPCs showed 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 revealed specific upregulation of inflammatory gene profiles in discrete, transient HSC populations, that propagated expansion of lymphoid-biased progenitors. Beyond fetal development, MIA caused 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 trajectory of output and function of fetal-derived immune cells by reshaping fetal HSC establishment.

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Apostol, A. C., Lopez, D. A., Lebish, E. J., Valencia, C. H., Romero-Mulero, M. C., Pavlovich, P., Hernandez, G. E., Forsberg, E. C., Cabezas-Wallscheid, N., Beaudin, A. E.. 2022-05-09. Prenatal inflammation perturbs fetal hematopoietic development and causes persistent changes to postnatal immunity. https://doi.org/10.1101/2022.05.08.491095

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