Selective vulnerability of cerebral vasculature to NOTCH3 variants in small vessel disease and rescue by phosphodiesterase-5 inhibitor

NOTCH3 variants cause CADASIL, the most common genetic form of small vessel disease (SVD) and vascular dementia (VaD), and increase the stroke and SVD/VaD risk. CADASIL is a systemic vasculopathy but predominantly manifests in the brain. The molecular mechanisms of CADASIL remain largely unclear with no specific available treatments. NOTCH3 is primarily expressed in vascular smooth muscle cells (VSMCs). Using human induced pluripotent stem cell (iPSC) models and developmental lineage-specific VSMC differentiation, we revealed a selective vulnerability of cerebral but not peripheral VSMC mimics to NOTCH3 variants. Transcriptomic, protein and functional analyses demonstrated a switching of CADASIL iPSC-VSMCs from a contractile to a synthetic phenotype, accompanied with extensive extracellular matrix accumulation and impairment of cell adhesion leading to anoikis. Importantly, we describe an endothelial independent nitric oxide signalling in VSMCs which was dysregulated in the CADASIL iPSC..., We resize the input image to 512×512 pixels. Then, the standard Canny edge detection algorithm is employed to outline the edges of stress fibers. Technically speaking, a Gaussian filter is applied to smooth the image whilst reducing noise. Afterwards, image gradients are computed so that potential edges can be identified.
, # Data from: Selective vulnerability of cerebral vasculature to NOTCH3 variants in small vessel disease and rescue by phosphodiesterase-5 inhibitor

Dataset DOI: [10.5061/dryad.2280gb66p](https://doi.org/10.5061/dryad.2280gb66p)

## Description of the data and file structure

This Code is for the paper titled 'Selective vulnerability of cerebral vasculature to NOTCH3 variants in small vessel disease and rescue by phosphodiesterase-5 inhibitor'. It is permanently open and free to read/download for the entire research community (no access code is needed).

1.'`C224Y.zip`':The data contains the stress fiber samples used in this article, including one folder labeled 'C224Y'. The results of stress fiber identification for each image, including image edges and cell nuclei, are stored in the 'image' folder, while the rest of the data contains various parameters such as detected coordinates and spatial dispersion.

C224Y:

The images in this folder were captured to examine the distribution of t..., ,