Rich, C. | Search bioRxiv

bioRxiv2018

Discordant perturbations of transcriptome and epigenome landscapes highlight dual roles of proinflammatory players in normal and IL1B-compromised OPC maturation trajectory in a prenatal model of diffuse white matter injury

Inflammatory insults accompanying prematurity provokes diffuse white matter injury (DWMI) which is associated with increased risk of neurodevelopmental disorders: pre-term infants have a 10 to 18-fold increased risk of developing autism spectrum disorders, compared to term infants. DWMI is due to maturation arrest in oligodendrocyte precursor cells (OPCs). Using integrated genome-wide approaches in a validated mouse perinatal model of DWMI, induced by systemic- and neuro-inflammation based on repeated interleukin-1B administrations, we show that neuroinflammation induces limited epigenomic disturbances in OPCs. In contrast, we unravel marked transcriptomic alterations of genes of the immune/inflammatory pathways, which are expressed in unstressed OPCs and physiologically downregulated along OPC maturation. Consistently, we observe that transcription factors of the inflammatory pathways occupy DNA both in unstressed and inflamed OPCs. Thus, rather than altering genome-wide chromatin accessibility, neuroinflammation takes advantage of open chromatin regions and deeply counteracts the stage-dependent downregulation of these active transcriptional programs. Therefore, our study opens new avenues for the future development of targeted approaches to protect preterm brains. Highlights{circ} Limited epigenomic impact of inflammation on OPC maturation blockade {circ}Major transcriptomic disturbances take advantage of a primed epigenetic landscape {circ}Proinflammatory genes are active in OPCs and downregulated upon maturation {circ}Neuroinflammation counteracts both this downregulation and maturation in OPCs

developmental biology↗

bioRxiv2018

Cell type identity determines transcriptomic immune responses in Arabidopsis thaliana roots.

Root pathogens are a major threat in global crop production and protection strategies are required to sustainably enhance the efficiency of root immunity. Our understanding of root immunity is still limited relative to our knowledge of immune responses in leaves. In an effort to reveal the organisation of immunity in roots, we undertook a cell type-specific transcriptome analysis to identify gene networks activated in epidermis, cortex and pericycle cells of Arabidopsis roots upon treatment with two immunity elicitors, the bacterial microbe-associated molecular pattern flagellin, and the endogenous damage-associated molecular pattern Pep1. Our analyses revealed that both elicitors induced immunity gene networks in a cell type-specific manner. Interestingly, both elicitors did not alter cell identity-determining gene networks. Using sophisticated paired motif promoter analyses, we identified key transcription factor pairs involved in the regulation of cell type-specific immunity networks. In addition, our data show that cell identity networks integrate with cell immunity networks to activate cell type-specific immune response according to the functional capabilities of each cell type.\n\nMaterial Distribution FootnoteThe author responsible for distribution of materials integral to the findings presented in this article in accordance with the policy described in the Instructions for Authors (www.plantcell.org) is: Patrick Schafer (p.schafer@warwick.ac.uk).

plant biology↗