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Tripartite factors leading to molecular divergence between human and murine smooth muscle
- Source :
- PLoS ONE, Vol 15, Iss 1, p e0227672 (2020), PLoS ONE
- Publication Year :
- 2020
- Publisher :
- Public Library of Science (PLoS), 2020.
-
Abstract
- A large number of pre-clinical and developmental investigations involve experimental vertebrate animals, of which mice have emerged as a favored organism. Recognition of the differences between humans and mice is essential for assessment of the relevance of animal studies to humans. The primary purpose of this study was to gauge the conservation between human and mouse vascular smooth muscle cell (VSMC) proteins mined from an analysis of the Human Protein Atlas. Two comparison were made: a) immunohistochemistry for 16 proteins in brain, heart, esophagus, bladder, stomach, lung, kidney, and aorta enabled comparison between human and mouse of protein localization in VSMC and non-vascular SMC; and b) multi-species primary protein sequence analysis of an expanded set vascular molecules enabled comparison between VSMC sequences among vertebrate species. In total, three dimensions of diversity were uncovered. First, a significant number of factors show human/mouse differences in cellular expression; these differences occurred in both VSMC and non-vascular SMC in an organ and cell-type dependent fashion. Many markers demonstrated notable cell-to-cell and regional heterogeneity in VSMC of the aorta and non-vascular SMC of the esophagus, bladder, and stomach. Second, species specificity can arise by genetic deletions as exemplified by the human protein adipogenesis regulatory factor (ADIRF), which is not present due to a large sequence gap in mice. Third, we describe significant cross-species protein sequence divergence in selected VSMC proteins which may result in altered orthologue function. In a sample of 346 vascular molecules, 15% demonstrate incomplete vertebrate species gene conservation. Divergence of predicted human/mouse VSMC protein sequences is higher than for endothelial proteins in all species examined. In the future, each of these three cross-species differences could be neutralized using gene manipulation, resulting in improved translational potential of murine experimental models.
- Subjects :
- 0301 basic medicine
Vascular smooth muscle
Swine
Muscle Proteins
Muscle, Smooth, Vascular
Conserved sequence
Mice
Orangutans
0302 clinical medicine
Myocyte
Tissue Distribution
Monotremes
Databases, Protein
Conserved Sequence
Mammals
Multidisciplinary
Eukaryota
Animal Models
Protein subcellular localization prediction
Immunohistochemistry
Cell biology
Experimental Organism Systems
Adipogenesis
Vertebrates
Apes
cardiovascular system
Medicine
Research Article
Primates
Science
Myocytes, Smooth Muscle
Human Protein Atlas
Mouse Models
Biology
Research and Analysis Methods
03 medical and health sciences
Model Organisms
Dogs
Species Specificity
Animals
Humans
Platypus
Gene
Immunohistochemistry Techniques
Organisms
Genetic Variation
Biology and Life Sciences
Muscle, Smooth
Histochemistry and Cytochemistry Techniques
030104 developmental biology
Amniotes
Animal Studies
Cats
Immunologic Techniques
030217 neurology & neurosurgery
Function (biology)
Biomarkers
Subjects
Details
- Language :
- English
- ISSN :
- 19326203
- Volume :
- 15
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- PLoS ONE
- Accession number :
- edsair.doi.dedup.....38aeae55254cd36ebcc6202acdb0d8f5