Abstract
Although great efforts to characterize the embryonic phase of brain microvascular system development have been made, its postnatal maturation has barely been described. Here, we compared the molecular and functional properties of brain vascular cells on postnatal day (P)5 vs. P15, via a transcriptomic analysis of purified mouse cortical microvessels (MVs) and the identification of vascular-cell-type-specific or -preferentially expressed transcripts. We found that endothelial cells (EC), vascular smooth muscle cells (VSMC) and fibroblasts (FB) follow specific molecular maturation programs over this time period. Focusing on VSMCs, we showed that the arteriolar VSMC network expands and becomes contractile resulting in a greater cerebral blood flow (CBF), with heterogenous developmental trajectories within cortical regions. Samples of the human brain cortex showed the same postnatal maturation process. Thus, the postnatal phase is a critical period during which arteriolar VSMC contractility required for vessel tone and brain perfusion is acquired and mature.
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Data availability
Transcriptomic data are openly available in the GEO repository (www.ncbi.nlm.nih.gov/geo/) under the accession number GSE173844. Oher data that support the findings of this study are available on request from the corresponding author.
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Acknowledgements
This work was funded by grants from the Association Européenne contre les Leucodystrophies (ELA) (ELA2012-014C2B), the Fondation pour la Recherche Médicale (FRM) (AJE20171039094) and the Fondation Maladies Rares (20170603). A. Gilbert’s PhD fellowship was funded by the FRM (PLP20170939025p60) and ELA (ELA2012-014C2B). L. Slaoui’s fellowship PhD was funded by the Ecole Normale Supérieure. A.-C. Boulay’s work was funded by the FRM (AJE20171039094) and the Foundation pour la recherche sur la sclérose en plaques (ARSEP). Despite our efforts, our work has not received any support from the French National Agency for Research (ANR).
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Conceptualization, MC-S. and A-CB; Methodology, MC-S, A-CB, PM, GL, AG, NR, DV, AR; Investigation, LS, AG, BD-P, MBL, LF, SC, AR, AC, QG, MF, KD, LJ, SA, A-CB, MC-S; Writing—Original Draft, MC-S; Funding Acquisition, MC-S.; Supervision, MC-S. and A-CB.
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429_2022_2592_MOESM1_ESM.xlsx
Supplementary Table S1 Dataset of the comparison of cortical MV transcriptomes on P5 and P15 Selected mRNAs have a mean number of reads ≥ 50 in at least one condition. The fold-change (FC) between expression on P5 and P15 and associated adjusted p-values (padj) are indicated. Base mean: mean reads for each transcript. n=3 libraries for each stage. file1 (XLSX 2599 KB)
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Supplementary Table S2 Pathway/Gene ontology data sets In cortical MVs, the “biological process” GO, KEGG and Reactome pathways significantly changed between P5 and P15. file2 (XLSX 69 KB)
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Supplementary Table S3 Identification of vascular-cell-type-specific or -preferentially expressed transcripts Cell-type-specific or -preferentially expressed transcripts are listed for each cluster. Left-hand columns: identification of transcripts -preferentially expressed in or specific to each cell. Middle columns: % of single-cells within and outside each cluster expressing the transcript logFC of expression difference between cells of the cluster and outside and the associated adjusted p-values. Right-hand columns: cortical MV RNA-Seq analysis. Log2FC on P15 versus P5 and the associated adjusted p-values. EC, endothelial cell; PC, pericyte; FB, fibroblast: VSMC, vascular smooth muscle cell file3 (XLSX 34 KB)
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Slaoui, L., Gilbert, A., Rancillac, A. et al. In mice and humans, brain microvascular contractility matures postnatally. Brain Struct Funct 228, 475–492 (2023). https://doi.org/10.1007/s00429-022-02592-w
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DOI: https://doi.org/10.1007/s00429-022-02592-w