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Review
. 2024 Jan;34(1):58-71.
doi: 10.1016/j.tcb.2023.06.001. Epub 2023 Jul 18.

Pericytes in the disease spotlight

Hielke van Splunder  1 , Pilar Villacampa  2 , Anabel Martínez-Romero  1 , Mariona Graupera  3
Affiliations
Review

Pericytes in the disease spotlight

Hielke van Splunder et al. Trends Cell Biol. 2024 Jan.

Abstract

Pericytes are known as the mural cells in small-caliber vessels that interact closely with the endothelium. Pericytes play a key role in vasculature formation and homeostasis, and when dysfunctional contribute to vasculature-related diseases such as diabetic retinopathy and neurodegenerative conditions. In addition, significant extravascular roles of pathological pericytes are being discovered with relevant implications for cancer and fibrosis. Pericyte research is challenged by the lack of consistent molecular markers and clear discrimination criteria versus other (mural) cells. However, advances in single-cell approaches are uncovering and clarifying mural cell identities, biological functions, and ontogeny across organs. We discuss the latest developments in pericyte pathobiology to inform future research directions and potential outcomes.

Keywords: fibrosis; pericrine signaling; pericyte; vascular disease.

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Conflict of interest statement

Declaration of interests The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Schematic representation of mural cell zonation in the adult mouse brain. (A) Localization on the arteriovenous axis, and (B) transcriptional gene expression of common molecular markers associated with mural cells. Brain mural cells are classified into distinct phenotypic gradients (indicated by the black arrows): arterial smooth muscle cells (aSMCs) with arteriole SMCs (aaSMCs), and capillary pericytes with venous SMCs (veSMCs). Mural cells located on venules are transcriptionally similar to pericytes and are hence referred to as venular pericytes (vPCs). Compared to pericytes and veSMCs, aSMCs and aaSMCs express high amounts of contractility genes such as Tagln, Acta2, Myh11, and Cnn1 (in red). Kcnj8, Abcc9, and Vtn (in yellow) are examples of markers most specific for pericytes, although they are also expressed by veSMCs (in green). Of note, canonical markers Anpep and Cd248 are specific for brain pericytes but lose their predictive value in most other tissues, indicative of organotypic specialization. The markers Pdgfrb, Cspg4, Rgs5, and Notch3 demonstrate broad expression in all mural cells and appear to be most conserved.
Figure 2
Figure 2
Organotypic heterogeneity of pericyte markers. This figure summarizes top-ranked pericyte markers in the brain, heart, lung, kidney, and colon of mouse (upper row) and human (lower row). Pericyte markers were chosen based on a stringent evaluation of transcriptional abundance, specificity, and homogeneity utilizing information provided by single-cell RNA sequencing (scRNA-seq) data [6., 7., 8.,50,82,84,85,95,100., 101., 102.]. Validation of the selected markers by in situ analysis was used as a second criteria for their selection.
Figure 3
Figure 3
Dysfunctional pericytes in disease. This figure illustrates a compendium of pathological features associated with pericytes which have been shown to contribute to disease onset/progression. Alterations include cell-intrinsic processes (cell death, defective migration, and metabolic reprogramming), reduced functionality (increased transcytosis and altered contractility), and altered environmental interactions [extracellular matrix (ECM) remodeling, immunomodulation, and enhanced tumorigenesis].
Figure 4
Figure 4
Pericytes as a source of myofibroblasts in fibrosis. Schematic illustration showing how, under stress conditions, pericytes detach from vessels and undergo a transition towards highly contractile, extracellular matrix (ECM)-producing myofibroblasts. The relative contributions of pericytes versus fibroblasts in a given context remains a topic of ongoing debate and investigation. Pericytes and fibroblasts may play different roles in fibrosis depending on several factors, including the anatomical location, local microenvironment, source of injurious stimuli, and technical biases.
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