Prenatal inflammation perturbs fetal hematopoietic development and causes persistent changes to postnatal immunity
Prenatal inflammation perturbs fetal hematopoietic development and causes persistent changes to postnatal immunity
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.
Cabezas-Wallscheid Nina、Apostol April C.、Valencia Clint H.、Forsberg E. Camilla、Beaudin Anna E.、Romero-Mulero Mari Carmen、Pavlovich Polina、L¨?pez Diego A.、Hernandez Gloria E.、Lebish Eric J.
Max Planck Institute of Immunobiology and EpigeneticsQuantitative and Systems Biology Graduate Program, University of California-MercedDivision of Microbiology and Immunology, Department of Pathology, University of Utah School of MedicineInstitute for the Biology of Stem Cells, University of California-Santa CruzDivision of Hematology and Hematologic Malignancies, Department of Internal Medicine, University of Utah School of MedicineMax Planck Institute of Immunobiology and EpigeneticsMax Planck Institute of Immunobiology and EpigeneticsDivision of Microbiology and Immunology, Department of Pathology, University of Utah School of MedicineMolecular Biology Institute, University of California - Los AngelesDepartment of Molecular and Cell Biology, University of California-Merced
基础医学生理学
hematopoiesisfetal developmentheterogeneityimmunityin utero inflammation
Cabezas-Wallscheid Nina,Apostol April C.,Valencia Clint H.,Forsberg E. Camilla,Beaudin Anna E.,Romero-Mulero Mari Carmen,Pavlovich Polina,L¨?pez Diego A.,Hernandez Gloria E.,Lebish Eric J..Prenatal inflammation perturbs fetal hematopoietic development and causes persistent changes to postnatal immunity[EB/OL].(2025-03-28)[2025-05-10].https://www.biorxiv.org/content/10.1101/2022.05.08.491095.点此复制
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