Dataset Information

ScRNAseq dataset of PDGFRβ+ cells in fibrosing skin and kidney with or without ZFYVE9/SARA overexpression

ABSTRACT: Activated myofibroblasts play an essential role in tissue fibrogenesis by producing extracellular matrixes (ECM). ECMs replace normal functioning tissue, reducing tissue plasticity and impairing functions of the organ. Recent studies suggested that pericytes are a major source of myofibroblast precursors. We previously showed that Smad Anchor for Receptor Activation (SARA) prevents cellular phenotypic transdifferentiation toward mesenchymal cells, and depletion of SARA induces transdifferentiation of epithelial cells to fibroblast-like phenotype. Here, we generated a transgenic mice that overexpress SARA specifically pericytes by using PDGFRβ-Cre (SARATg, PDGFRβ-Cre). When subjected to either subcutaneous injection of bleomycin or intraperitoneal administration of aristolochic acid, which induces skin and kidney fibrosis, respectively, SARATg, PDGFRβ-Cre mice developed significantly less fibrosis compared to SARAWT, PDGFRβ-Cre mice. To decipher molecular signature and pericyte trajectory under fibrotic conditions and effects of SARA overexpression, we isolated PDGFR+ cells from skin or kidney of SARATg or WT, PDGFRβ-Cre, Z/EG mice with or without fibrotic stimuli and performed scRNAseq analyses. In both skin and kidney sample sets, we found pericytes and immune cell populations are the major cell components among the PDGFR+ GFP+ cells. We found that pericyte populations are divided into canonical and non-canonical sub-populations and the latter has assumed myofibroblast characteristics. Trajectory mapping revealed a single path from canonical to non-canonical pericyte sub-populations and SARA overexpression truncated the trajectory. These results suggest that SARA prevents pericyte transdifferentiation into myofibroblasts under fibrotic condition, and therefore anti-fibrotic.

ORGANISM(S): Mus musculus

PROVIDER: GSE211810 | GEO | 2022/11/23

REPOSITORIES: GEO

ACCESS DATA

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Project description:Pericytes are multifunctional contractile cells that reside on capillaries. Pericytes are critical regulators of cerebral blood flow and blood-brain barrier function, and pericyte dysfunction may contribute to the pathophysiology of human neurological diseases including Alzheimer’s disease, multiple sclerosis, and stroke. Induced pluripotent stem cell (iPSC)-derived pericytes (iPericytes) are a promising tool for vascular research. However, it is unclear how iPericytes functionally compare to primary human brain vascular pericytes (HBVPs). We differentiated iPSCs into iPericytes of either the mesoderm or neural crest lineage using established protocols. We compared iPericyte and HBVP morphologies, quantified gene expression by qPCR and bulk RNA sequencing, and visualised pericyte protein markers by immunocytochemistry. To determine whether the gene expression of neural crest iPericytes, mesoderm iPericytes or HBVPs correlated with their functional characteristics in vitro, we quantified EdU incorporation following exposure to the key pericyte mitogen, platelet derived growth factor (PDGF)-BB and, contraction and relaxation in response to the vasoconstrictor endothelin-1 or vasodilator adenosine, respectively. iPericytes were morphologically similar to HBVPs and expressed canonical pericyte markers. Consistent with the ability of HBVPs to respond to PDGF-BB signalling, PDGF-BB enhanced and PDGF receptor (PDGFR)β inhibitors impaired iPericyte proliferation. Administration of endothelin-1 led to iPericyte contraction and adenosine led to iPericyte relaxation, of a magnitude similar to the response evoked in HBVPs. We determined that neural crest iPericytes were less susceptible to PDGFRβ inhibition, but responded most robustly to vasoactive meditators. iPericytes express pericyte-associated genes and proteins and, exhibit an appropriate physiological response upon exposure to a key endogenous mitogen or vasoactive mediators. Therefore, this protocol to generate functional iPericytes would be suitable for use in future investigations exploring pericyte function or dysfunction in neurological diseases.

Dataset Information

ScRNAseq dataset of PDGFRβ+ cells in fibrosing skin and kidney with or without ZFYVE9/SARA overexpression

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets