In the MATRIXOME project, we launched body-wide expression profiling of the basement membrane, an extracellular matrix specialized for epithelial, endothelial and muscle tissues, on the basis of immunohistochemistry. We have analyzed expression patterns of 42 ECM proteins (36 basement membrane proteins plus 6 other ECM proteins partially localizing at the basement membranes) in whole mouse embryos on standardized experimental platforms. The resulting dataset contains body-wide expression profiles of about 80% of all known basement membrane proteins that have been identified so far. The immunohistochemical data have been converted to hundreds of high resolution digital slides and compiled in the MOUSE BASEMENT MEMBRANE BODYMAP. This MOUSE BASEMENT MEMBRANE BODYMAP provides a bird's-eye view of the cell- and tissue-specific customization of the extracellular microenvironment and should contribute to not only extracellular matrix biology but also regeneration medicine and tissue engineering by providing a molecular basis for the reconstitution of optimized scaffolds.

Extracellular matrix and matrixome

The proliferation and differentiation of cells in multicellular organisms are strictly regulated by cues transmitted from the extracellular environment. Extracellular matrix (ECM) is a supramolecular assembly forming fibrillar or sheet-like meshwork outside cells and provides a framework of the extracellular environment that serves as a scaffold to which cells adhere. ECM also regulates a wide range of cell behaviors including cell growth, differentiation, migration and survival via transducing signals into cells through a variety of cell surface ECM receptors, e.g., integrins, in collaboration with signals transduced from growth factors and other soluble factors. Although ECMs are wide-spread tissue components, their fine structure and composition varies from tissue to tissue, as well as within the same tissue at different locations, different developmental periods and during tissue repair. Thus, individual cell types are supposed to have their own customized extracellular environment, or so-called 'niche', to sustain their potentials in proliferation, differentiation, and self-renewal. Despite the importance of understanding the extracellular microenvironment of a given tissue/cell type as a whole, the information defining the ECM constituents of a given tissue/cell type is only fragmentary.

We propose the term 'matrixome' as a subset of the proteome to define whole collections of ECM molecules that constitute the customized microenvironments of individual cell types. To uncover the matrixome of individual cell and tissue types, we performed a comprehensive screening for novel ECM proteins using RIKEN FANTOM mouse cDNA collections as a source and launched a body-wide expression profiling of ECM proteins on the basis of immunohistochemistry. The dataset of expression profiles of basement membrane proteins including 5 novel ones identified in this project has been compiled in the MOUSE BASEMENT MEMBRANE BODYMAP.

Basement membrane is a thin sheet of ECM that underlies epithelial cells and surrounds muscle, fat and peripheral nerve cells and blood vessels. Given that the parenchymal cells of many organs and their stem cells are of epithelial origin, the basement membrane plays a premier role as the microenvironment for the maintenance of differentiated phenotypes as well as the regulation of proliferation of parenchymal cells. The importance of the basement membrane is also underscored in epithelial-mesenchymal interactions during development.

The major components of basement membranes are laminins, type IV collagens, nidogens and the heparan sulfate proteoglycan perlecan. Laminins and type IV collagens display significant molecular diversities due to their distinct subunit compositions. Besides these major components, at least 26 distinct constituents including 7 new ones identified in our project have been found in basement membranes. The construction of body-wide expression profiles of the basement membrane components included: i) production of antibodies against known and novel basement membrane proteins and confirmation of their specificities; ii) optimization of the staining conditions for individual antibodies; iii) preparation of tissue/organ specimens on a standardized platform and iv) compilation of the immunohistochemical images into a database.

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