Anatomic Demarcation by Positional Variation in Fibroblast Gene Expression Programs 英文参考文献.docVIP

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Anatomic Demarcation by Positional Variation in Fibroblast Gene Expression Programs 英文参考文献.doc

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Anatomic Demarcation by Positional Variation in Fibroblast Gene Expression Programs 英文参考文献

AnatomicDemarcationbyPositionalVariation inFibroblastGeneExpressionPrograms John L.Rinn1,Chanda Bondre2,Hayes B.Gladstone1,Patrick O.Brown2,3*,Howard Y.Chang1* 1 Program in Epithelial Biology, Department of Dermatology, Stanford University School of Medicine, Stanford, California, United States of America, 2 Department of Biochemistry, Stanford University School of Medicine, Stanford, California, United States of America, 3 Howard Hughes Medical Institute, Stanford University School of Medicine,Stanford,California,UnitedStatesofAmerica Fibroblasts are ubiquitous mesenchymal cells with many vital functions during development, tissue repair, and disease. Fibroblasts fromdifferentanatomic sites havedistinct andcharacteristic geneexpression patterns,but the principles that govern their molecular specialization are poorly understood. Spatial organization of cellular differentiation may be achieved by unique specification of each cell type; alternatively, organization may arise by cellsinterpretingtheirpositionalongacoordinatesystem.Herewetestthesemodelsbyanalyzingthegenome-wide geneexpressionprofilesofprimaryfibroblastpopulationsfrom43uniqueanatomicalsitesspanningthehumanbody. Large-scaledifferencesinthegeneexpressionprogramswererelatedtothreeanatomicdivisions:anterior-posterior (rostral-caudal), proximal-distal, and dermal versus nondermal. A set of 337 genes that varied according to these positional divisions was able to group all 47 samples by their anatomic sites of origin. Genes involved in pattern formation, cell-cell signaling, and matrix remodeling were enriched among this minimal set of positional identifier genes. Many important features of the embryonic pattern of HOX gene expression were retained in fibroblasts and were confirmed both in vitro and in vivo. Together, these findings suggest that site-specific variations in fibroblast gene expression programs are not idiosyncratic but rather are systematically related to their positional identities relativ