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The mesenchymal cell-specific proteomeThe mesenchymal cell transcriptomeAdipocytesFibro-adipogenic progenitorsFibroblastsStellate cellsStromal cellsOther mesenchymal cellsThe Mesenchymal cell functionBackgroundRelevant links and publications
Single cell type methods
The mesenchymal cell-specific proteomeMesenchymal cells are a diverse group of cells that originate from mesenchymal stem cells. The differentiated forms of mesenchymal cells have important roles in various types of connective tissues in which they perform a variety of functions, including; extracellular matrix organization, immune response, wound healing and formation of bone and cartilage. Transcriptome analysis shows that 67% (n=13603) of all human proteins (n=20162) are detected in mesenchymal cells and 1216 of these genes show an elevated expression in any mesenchymal cells compared to other cell type groups. In-depth analysis of the elevated genes in mesenchymal cells using scRNA-seq and antibody-based protein profiling allowed us to visualize the expression patterns of these proteins in the following types of mesenchymal cells: adipocytes, fibro-adipogenic progenitors, fibroblasts, stellate cells and stromal cells. The mesenchymal cell transcriptomeThe scRNA-seq-based mesenchymal cell transcriptome can be analyzed with regard to specificity, illustrating the number of genes with elevated expression in each specific mesenchymal cell type compared to other cell types (Table 1). Genes with an elevated expression are divided into three subcategories:
AdipocytesAdipocytes are the main cell type present in adipose tissue and are responsible for storing calories in the form of lipid droplets. Besides lipid storage, the adipocytes also have an endocrine function by secreting adipokines. As shown in the table1, 272 genes show elevated expression in adipocytes compared to other grouped cell types, while 565 genes show elevated expression in adipocytes compared to all 154 other cell types (table 2). Examples of genes are PLIN1 involved in coating lipid droplets in cells and LIPE a lipase able to hydrolyze a broad number of different substrates. Table 2. Number of genes in the subdivided specificity categories of elevated expression in adipocytes compared to other cell types.
Fibro-adipogenic progenitorsFibro-adipogenic progenitors are mesenchymal progenitors in muscle that can become fibroblasts or adipocytes. They support muscle regeneration but can drive fibrosis or fat infiltration after injury. As shown in the table, 431 genes show elevated expression in Fibro-adipogenic progenitors compared to other cell types.
FibroblastsFibroblasts are found ubiquitously throughout the body except for the brain. They are the main and prototypic mesenchymal cell type that produces collagen fibers, glycosaminoglycans, reticular and elastic fibers, which constitute the basic structural framework of connective tissue. Besides their structural function in extracellular matrix synthesis, they also play a critical role in the response to a tissue injury such as immune response and wound healing.
Stellate cellsStellate cells are perisinusoidal liver cells that store vitamin A and regulate extracellular matrix. When activated after injury they become myofibroblastic and can cause fibrosis. As shown in the table, 365 genes show elevated expression in stellate cells compared to other cell types.
Stromal cellsStromal cells provide structural and functional support to surrounding tissues, regulating cellular interactions, hormone responses, and tissue remodeling. In the ovary, endometrium, decidua, and thymus, these cells contribute to reproductive cycling, pregnancy maintenance, and immune regulation through secretion of signaling molecules and extracellular matrix components.
Peritubular myoid cellsThe spermatogenesis takes place in the seminiferous tubules, a compartment that is surrounded by a wall made of peritubular cells and extracellular matrix. The peritubular cells are involved in the contraction of the seminiferous tubules to help move the spermatozoa. As shown in the table, 363 genes show elevated expression in peritubular cells compared to other cell types. Genes elevated in peritubular cells include smooth muscle alpha actin (ACTA2), encoding a protein highly expressed in the peritubular structure. Another example is fibulin-5 (FBLN5), which is a secreted protein that forms elastic fibers found in the extracellular matrix with various functions such as providing strength and flexibility of the connective tissue.
Ovarian stromal cellsThe ovarian stromal cells are a heterogenous group of incompletely characterized fibroblast-like, spindle-shaped and interstitial cells that produce and organize the ECM components surrounding the oocyte-containing ovarian follicles in order to facilitate the oogenesis, including proteins involved in structural support and the synthesis of steroid hormones. As shown in the table, 238 genes show elevated expression in ovarian stromal cells compared to other cell types. An example of a protein with elevated expression in ovarian stromal cells that is involved in the steroidogenesis is retinol binding protein 1 (RBP1), which binds to and transports retinol, also known as vitamin A, an important component in the synthesis of steroid hormones.
Endometrial stromal cellsThe endometrial stromal layer is the largest compartment of the endometrium, which comprises uterine fibroblasts and a mix of immune cells. Through hormones and immune cells it controls the proliferation, remodeling and breakdown of the tissue during the menstrual or estrous cycle. The endometrial stromal cells can also quickly evolve into decidualized cells when activated by an implanting blastocyst. As shown in the table, 266 genes show elevated expression in endometrial stromal cells compared to other cell types. An example of a protein with elevated expression in endometrial stromal cells is homeobox A11 (HOXA11), which is is suggested to play an important role in proliferation, differentiation and receptivity of the tissue.
Decidual stromal cellsDecidual stromal cells are actually maternal cells in the uterine lining (decidua) rather than part of the placenta itself. They differentiate from endometrial stromal cells during early pregnancy and play essential roles in supporting implantation, modulating the maternal immune response, and facilitating placental development by interacting with invading trophoblasts. As shown in the table, 500 genes show elevated expression in decidual stromal cells compared to other cell types. An example of a protein with elevated expression in decudual stromal cells is IGFBP1.
Thymic myoid cellsThymic myoid cells are muscle‑like cells in the thymus expressing contractile proteins. They present muscle antigens and may aid negative selection of autoreactive T cells. As shown in the table, 487 genes show elevated expression in thymic myoid cells compared to other cell types. Other mesenchymal cellsThere are additional mesenchymal cells in the body that currently lack scRNA-seq data at Human Protein Atlas. Osteoblasts are cuboidal mononuclear cells specialized in bone development and homeostasis by synthesizing bone matrix components that are progressively mineralized through regulation of calcium and phosphate in the area. Type 1 collagen (encoded by the genes COL1A1 and COL1A2) is the most abundant ECM protein produced by osteoblasts. Chondroblasts are cells important in forming chondrocytes and cartilage matrix, and once the chondroblasts are embedded in the cartilage matrix they are called chondrocytes. These cells are localized in the perichondrium, which is a dense irregular layer of connective tissue that surrounds the cartilage. Type II collagen (COL2A1) is the major component of the cartilage matrix. Aggrecan (ACAN) is an integral part of the extracellular matrix in cartilaginous tissue and it withstands compression in cartilage.
The Mesenchymal cell functionAdipose cells are mainly localized in adipose tissue as well as other loose connective tissues present under the skin and around the organs where it functions as a physical protective cushion. Protecting the underlying tissues is not the only function of adipose cells as these are also known to store lipids as well as have an endocrine function. Adipocytes take up and store lipids as triglyceride-rich lipoproteins in a lipid droplet which can be consumed during periods of low energy, effectively functioning as a battery for the body. The endocrine function of adipose cells is their secretion of adipokines like leptin, resistin, and adiponectin important for regulating lipid metabolism, insulin sensitivity, and the immune system. Dysregulation of this endocrine function, for example due to obesity, is linked to cardiovascular disorders, insulin resistance, and chronic inflammation. Fibroblasts, peritubular cells and endometrial stromal cells all originate from mesenchymal stem cells and can therefore show morphologically similar fusiform structure, but they can also demonstrate similar functions since they all reside in connective tissue. The primary function of fibroblasts is to maintain the structural integrity within the connective tissue through the synthesis of collagen fibers, glycosaminoglycans and elastic fibers. In addition to extracellular matrix organization they also take part in the response to tissue injury. Peritubular cells surround the seminiferous tubules and are accepted to have a contractile function to help the move of spermatozoa and fluid. However, further studies are required to fully understand their function. Endometrial stromal cells are specialized in the sense that they can proliferate, remodel or break down the tissue depending on the menstrual or estrous cycle. Furthermore, endometrial stromal cells are also able to become decidualized, which is essential during pregnancy for the survival and development of the embryo. Other differentiated types of mesenchymal cells such as chondroblasts and osteoblasts have important specialized functions, including bone formation and energy storage. The histology of organs that contain mesenchymal cells, including interactive images, is described in the Protein Atlas Histology Dictionary. BackgroundHere, the protein-coding genes expressed in mesenchymal cells are described and characterized, together with examples of immunohistochemically stained tissue sections that visualize corresponding protein expression patterns of genes with elevated expression in different mesenchymal cell types. The transcript profiling was based on publicly available genome-wide expression data from scRNA-seq and snRNA-seq experiments (36 datasets) covering 34 tissues. All datasets (unfiltered read counts of cells) were clustered independenty using leiden clustering, resulting in a total of 1175 different cell type clusters. The clusters were then manually annotated based on a survey of known tissue and cell type-specific markers. The RNA-seq data from each cluster of cells was aggregated to mean normalized protein-coding counts per million (nCPM) for all protein-coding genes. A specificity and distribution classification was performed for both single cell types individually, as well as grouped into 53 main cell type groups. The specificity classification determined the number of elevated genes, while the distribution determined whether genes are detected in one, several or all cell types or cell type groups. It should be noted that since the analysis was limited to datasets representing 34 tissue types, not all human cell types are represented. Furthermore, some cell types are present only in low amounts, or identified only in mixed cell clusters, which may affect the results and bias the cell type specificity. Relevant links and publications Uhlén M et al., Tissue-based map of the human proteome. Science (2015) |
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