Dataset Information

Organizational hierarchy and structural diversity of microvascular pericytes in adult mouse cortex.

ABSTRACT: Smooth muscle cells and pericytes, together called mural cells, coordinate many distinct vascular functions. Canonically, smooth muscle cells are ring-shaped and cover arterioles with circumferential processes, whereas pericytes extend thin processes that run longitudinally along capillaries. In between these canonical mural cell types are cells with features of both smooth muscle cells and pericytes. Recent studies suggest that these transitional cells are critical for controlling blood flow to the capillary bed during health and disease, but there remains confusion on how to identify them and where they are located in the brain microvasculature. To address this issue, we measured the morphology, vascular territory, and α-smooth muscle actin content of structurally diverse mural cells in adult mouse cortex. We first imaged intact 3D vascular networks to establish the locations of major gradations in mural cell appearance as arterioles branched into capillaries. We then imaged individual mural cells occupying the regions within these gradations. This revealed two transitional cells that were often similar in appearance, but with sharply contrasting levels of α-smooth muscle actin. Our findings highlight the diversity of mural cell morphologies in brain microvasculature, and provide guidance for identification and categorization of mural cell types.

SUBMITTER: Grant RI

PROVIDER: S-EPMC6399730 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

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Organizational hierarchy and structural diversity of microvascular pericytes in adult mouse cortex.

Grant Roger I RI Hartmann David A DA Underly Robert G RG Berthiaume Andrée-Anne AA Bhat Narayan R NR Shih Andy Y AY

Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism 20170921 3

Smooth muscle cells and pericytes, together called mural cells, coordinate many distinct vascular functions. Canonically, smooth muscle cells are ring-shaped and cover arterioles with circumferential processes, whereas pericytes extend thin processes that run longitudinally along capillaries. In between these canonical mural cell types are cells with features of both smooth muscle cells and pericytes. Recent studies suggest that these transitional cells are critical for controlling blood flow to ...[more]

PMID: 28933255

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Project description:The microcirculation serves crucial functions in adult heart that are distinct from those carried out by epicardial vessels. Microvessels are also governed by unique regulatory mechanisms, impairment of which leads to microvessel-specific pathology. While great progress has been made in understanding and treating coronary artery disease (CAD), there are few treatment options for patients with microvascular heart disease, primarily due to our limited understanding of underlying pathology. The advent of high-throughput analytical approaches of mRNA and protein expression in specific cells provides an opportunity to transform our understanding of microvessel biology and disease at the molecular level. Understanding responses of individual microvascular cells to the same physiological or pathophysiological stimuli requires the ability to isolate the specific cell types that comprise the functional units of the microcirculation in an adult heart, preferably from the same heart, to ensure that different cells have been exposed to the same in-vivo conditions. Furthermore, in-vitro functional and molecular analysis requires an integrated workflow that combines primary cell culture with high-throughput proteomic or transcriptomic analysis. Our goal was an integrated process for simultaneous isolation, culture, and proteomic profiling of the three main cell types comprising the microcirculation in adult mouse heart: endothelial cells (ECs), pericytes (PCs) and vascular smooth muscle cells (VSMCs). We developed an integrated platform for simultaneous isolation and culture of ECs, PCs and VSMCs from adult mouse heart, coupled with unbiased mass spectrometry (MS)-based characterization of protein expression in these cells. We defined microvascular cell proteomes, identified novel protein markers and confirmed established cell-specific markers. Isolating and analyzing microvascular cell types separately from the same preparation of adult mouse hearts allowed for separate investigations into the unique contributions of the different cell types to health and disease, and interactions among different cell types.

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Dataset Information

Organizational hierarchy and structural diversity of microvascular pericytes in adult mouse cortex.

Publications

Organizational hierarchy and structural diversity of microvascular pericytes in adult mouse cortex.

Similar Datasets

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