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Single Cell Transcriptomic Analysis Reveals Organ Specific Pericyte Markers and Identities
Seung-Han Baek1, Enrico Maiorino2, Hyunbum Kim1
1Division of Pulmonary Medicine, Department of Pediatrics, Boston Children's Hospital and Harvard Medical School, Boston, MA, United States.
Insights
Researchers identified specific pericyte markers in mouse lung, heart, kidney, and bladder. These findings help distinguish pericytes from other mural cells, advancing our understanding of vascular biology and disease.
Area of Science:
- Vascular Biology and Cell Biology
- Genomics and Bioinformatics
- Tissue-specific cell identification
Background:
- Pericytes are crucial mural cells regulating vascular development and homeostasis.
- Understanding pericyte heterogeneity and function is limited by difficulties in distinguishing them from other mural cells.
- Existing knowledge gaps hinder the understanding of pericyte roles in physiology and pathology.
Purpose of the Study:
- To identify novel pericyte-specific markers across different tissues.
- To differentiate pericytes from other mural cell populations using single-cell RNA sequencing.
- To validate identified markers in human datasets and explore conserved markers.
Main Methods:
- Analysis of single-cell RNA sequencing data from mouse pericyte populations (Tabula Muris Senis).
- Identification of mural cell clusters expressing known pericyte markers (Cspg4, Pdgfrb).
- Differential gene expression analysis to find novel pericyte markers and validation in human databases.
Main Results:
- Defined pericytes as co-expressing Cspg4 and Pdgfrb.
- Identified novel tissue-specific pericyte markers: Kcnk3 (lung), Rgs4 (heart), Myh11/Kcna5 (kidney), Pcp4l1 (bladder), Higd1b (lung/heart).
- Validated mouse pericyte markers in human lung and heart datasets, revealing conserved markers.
Conclusions:
- Successfully identified specific pericyte markers in lung, heart, kidney, and bladder.
- Revealed differentially expressed genes and functional relationships among mural cells.
- Established a foundation for further research into pericyte biology and disease.
Abstract:
Pericytes are mesenchymal-derived mural cells that wrap around capillaries and directly contact endothelial cells. Present throughout the body, including the cardiovascular system, pericytes are proposed to have multipotent cell-like properties and are involved in numerous biological processes, including regulation of vascular development, maturation, permeability, and homeostasis. Despite their physiological importance, the functional heterogeneity, differentiation process, and pathological roles of pericytes are not yet clearly understood, in part due to the inability to reliably distinguish them from other mural cell populations. Our study focused on identifying pericyte-specific markers by analyzing single-cell RNA sequencing data from tissue-specific mouse pericyte populations generated by the Tabula Muris Senis. We identified the mural cell cluster in murine lung, heart, kidney, and bladder that expressed either of two known pericyte markers, Cspg4 or Pdgfrb. We further defined pericytes as those cells that co-expressed both markers within this cluster. Single-cell differential expression gene analysis compared this subset with other clusters that identified potential pericyte marker candidates, including Kcnk3 (in the lung); Rgs4 (in the heart); Myh11 and Kcna5 (in the kidney); Pcp4l1 (in the bladder); and Higd1b (in lung and heart). In addition, we identified novel markers of tissue-specific pericytes and signaling pathways that may be involved in maintaining their identity. Moreover, the identified markers were further validated in Human Lung Cell Atlas and human heart single-cell RNAseq databases. Intriguingly, we found that markers of heart and lung pericytes in mice were conserved in human heart and lung pericytes. In this study, we, for the first time, identified specific pericyte markers among lung, heart, kidney, and bladder and reveal differentially expressed genes and functional relationships between mural cells.
