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Maternal Immune Activation perturbs fetal hematopoietic development and causes persistent changes to postnatal immunity

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus

PROVIDER: GSE161927 | GEO | 2023/01/27

REPOSITORIES: GEO

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Maternal Immune Activation perturbs fetal hematopoietic development and causes persistent changes to postnatal immunity [scRNA-Seq']

Project description:Adult hematopoietic stem cells (HSCs) respond directly to inflammation and infection, resulting in both acute and persistent changes in quiescence, mobilization, and differentiation. Here we show that fetal HSCs respond to maternal inflammation in utero, and the fetal response drives long-term changes to postnatal hematopoiesis and immunity. Heterogeneous fetal hematopoietic stem and progenitor cells (HSPCs) show divergent responses to maternal immune activation (MIA), including changes in quiescence, expansion, and immune cell output. Single cell transcriptomic analysis of fetal HSPCs reveals specific upregulation of inflammation-responsive genes in discrete populations, in response to upregulated IFNα and IL-1α in the fetal liver cytokine milieu. Postnatally, MIA caused the inappropriate expansion and persistence of transient progenitors, concomitant with increased cellularity and hyper-responsiveness of fetal-derived immune cells. Our investigation demonstrates how inflammation in utero can direct the trajectory of hematopoiesis and immunity by reshaping fetal HSC establishment.

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Maternal Immune Activation perturbs fetal hematopoietic development and causes persistent changes to postnatal immunity [RNA-Seq]

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