Vascular Homeostasis and Inflammation in Health and Disease—Lessons from Single Cell Technologies
Abstract
:1. Introduction
2. Overview of Single Cell Analyses
3. Single Cell Technology towards Creation of a Comprehensive Vascular Cell Atlas
4. Vascular Inflammation
4.1. Atherosclerosis
4.1.1. Smooth Muscle Cells in Atherosclerosis
4.1.2. Immune Cells in Atherosclerosis
4.2. Cardiac Vasculature in Disease
4.3. Pulmonary Arterial Hypertension
4.4. Vascular Dysfunction in Neural Disorders
5. Outlook and Perspectives
5.1. Intercellular Communication
5.2. Single Cell Epigenetics
6. Concluding Remarks
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Cell Type | Marker Genes (scRNA-seq) |
---|---|
all ECs | Kdr (Vegfr2), Cdh5, Pecam1 (CD31), Tie1, Flt1, Vwf, Icam2 (CD102) |
arterial ECs | Hey1, Fbln5, Vegfc, Sema3g, Cytl1, Gkn3, Stmn2, Sox17, Bmx, Efnb2 |
venous ECs | Nr2f2, Lcn2, Vwf, Emcn, Scl38a5, Cfh, Apoe |
capillary ECs | Mfsd2a, Rgcc, Ramp3, Cd300lg, Tgfb2 (A), Glul (A), Tfrc (V), Car4 (V) |
lymphatic ECs | Flt4, Prox1, Mmm1, Ccl21a, Mmrn1, Fgl2, Lyve1, Thy1 |
all SMCs | Myh11, Acta2, Tagln, Vim, Des, Myl9, Pdgfrb, Cspg4, Tcf21 |
arterial SMCs | Cnn1 |
arteriole SMCs | Acta2, Tagln-high |
venous SMCs | Acta2, Tagln-low |
pericytes | Pdgfrb, Cspg4, Des, Abcc9, Vtn, Anpep, Rgs5 |
fibroblasts | Dcn, Tcf21, Bgn, Eln, Col1a1, Col1a2, Pdgfra |
Tissue, disease | Model | Main Finding | Reference |
---|---|---|---|
All vasculature | WT 8-week-old male C57BL6/J mice | Vascular cells show transcriptional heterogeneity that is organ-dependent and consistent with organ-specific specialization of vasculature. | [10] |
Mouse aorta Atherosclerosis | 12-week-old female C57/BL6 mice, 8 weeks of chow or Western diet | Detected three EC subpopulations in plaques and an increase in expression of contractile genes in ECs. | [47] |
Mouse aorta Atherosclerosis | 12-week-old male C57BL/6J WT and ApoE−/− mice, chow diet | Detected activation of immune cells; inflammatory and progenitor-like state of non-immune cells; existence of SCA1+ SMC population | [52] |
Mouse aorta Atherosclerosis | 8- to 14-week-old male mice; Myh11-reporter, Sca1-reporter, ApoE−/−, cholesterol rich diet | Found increase in SCA1+ SMC population in atherosclerotic mice. | [48] |
Mouse aorta Human aorta Atherosclerosis | Myh11-reporter, Myh11-driven Tcf21 knockout (and control), ApoE−/−, high fat diet. Human: 3♂, 1♀, proximal-to-mid right coronary artery | Performed SMC lineage-tracing. Showed importance of TFC21 in humans and mice for the trans-differentiation of SMCs into fibroblasts (“fibromyocyte”). | [49] |
Mouse aorta Atherosclerosis | 6- to 8-week-old Ldlr−/− C57BL/6J male mice, atherogenic diet; 8-week-old ApoE−/− female mice, Western diet | Identified three subpopulations of macrophages in plaques: resident, inflammatory Il1βhi, Trem2hi. | [50] |
Mouse aorta Atherosclerosis | ApoE−/−, Ldlr−/−, Cx3cr1-reporter, LysM-reporter C57BL6/J mice; D374Y-hPCSK9 transgenic mice, Western diet | Described heterogeneity of macrophages in plaques; Showed increased foamy macrophages as plaques increase in size. | [51] |
Mouse aorta Atherosclerosis | 8-week-old Cx3cr1-reporter mice, Western diet; recovery model – switch to a chow diet + injection of apolipoprotein B (ApoB) anti-sense oligonucleotide. | Performed tracing of Cx3cr1+ myeloid cells in plaque: Cd11b+ myeloid cells in the lesion; identified Trem2hi, DNase1l3hi, RetnlahiEarhi, IFN signaturehi, and “stem-cell like” macrophages. | [59] |
Mouse heart MI | 10- to 12-week-old male mice; myocardial infarction (MI) by permanent ligation of left anterior descending branch of the coronary artery; Wt1-reporter mice (epicardial tracing); Tek-reporter mice (endocardial tracing). | Post-MI: detected activation of fibroblasts, increase in myofibroblasts, occurrence of “matrifibrocyte” and increase in EC population. | [64] |
Mouse heart MI | 8 to 10-week-old Pdgfb-reporter mice; MI by permanent ligation of left anterior descending branch of the coronary artery. | Detected angiogenic, proliferative and pro-inflammatory EC subpopulations in border zone 7 days post-MI. | [67] |
Human lung PAH | Human lung samples: healthy (n = 6) and idiopathic pulmonary arterial hypertension (n = 3). | Showed increase in EC angiogenesis and ECM production by SMCs and pericytes. | [74] |
Mouse brain vasculature | 10- to 19-week-old, Cspg4-reporter, Pdgfrb-reporter, Pdgfra-reporter, Cldn5-reporter, Sm22-reporter C57BL6/J mice. | Identified 1798 transcripts associated with EC zonation. Showed pericytes are not zonated, but segregate into 2 major clusters. | [3] |
Developing mouse brain | E14.5 embryos, C57BL/6 background. | Identified 1710 unique ligand-receptor interactions between EC, pericytes, microglia and neural cells. | [19] |
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Bondareva, O.; Sheikh, B.N. Vascular Homeostasis and Inflammation in Health and Disease—Lessons from Single Cell Technologies. Int. J. Mol. Sci. 2020, 21, 4688. https://doi.org/10.3390/ijms21134688
Bondareva O, Sheikh BN. Vascular Homeostasis and Inflammation in Health and Disease—Lessons from Single Cell Technologies. International Journal of Molecular Sciences. 2020; 21(13):4688. https://doi.org/10.3390/ijms21134688
Chicago/Turabian StyleBondareva, Olga, and Bilal N. Sheikh. 2020. "Vascular Homeostasis and Inflammation in Health and Disease—Lessons from Single Cell Technologies" International Journal of Molecular Sciences 21, no. 13: 4688. https://doi.org/10.3390/ijms21134688