Project description:Data set to accompany : Anatomic demarcation by positional variation in fibroblast gene expression programs. PLoS Genet. 2006 Jul;2(7):e119. PMID: 16895450 Fibroblasts are ubiquitous mesenchymal cells with many vital functions during development, tissue repair, and disease. Fibroblasts from different anatomic sites have distinct and characteristic gene expression 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 cells interpreting their position along a coordinate system. Here we test these models by analyzing the genome-wide gene expression profiles of primary fibroblast populations from 43 unique anatomical sites spanning the human body. Large-scale differences in the gene expression programs were related to three anatomic divisions: 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 relative to major anatomic axes. Set of arrays organized by shared biological context, such as organism, tumors types, processes, etc. Computed
Project description:Data set to accompany : Anatomic demarcation by positional variation in fibroblast gene expression programs. PLoS Genet. 2006 Jul;2(7):e119. PMID: 16895450 Fibroblasts are ubiquitous mesenchymal cells with many vital functions during development, tissue repair, and disease. Fibroblasts from different anatomic sites have distinct and characteristic gene expression 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 cells interpreting their position along a coordinate system. Here we test these models by analyzing the genome-wide gene expression profiles of primary fibroblast populations from 43 unique anatomical sites spanning the human body. Large-scale differences in the gene expression programs were related to three anatomic divisions: 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 relative to major anatomic axes. Set of arrays organized by shared biological context, such as organism, tumors types, processes, etc. Keywords: Logical Set
Project description:Oncogenic alterations to DNA are not transforming in all cellular contexts. This may be due to pre-existing transcriptional programs in the cell of origin. Here, we define anatomic position as a major determinant of why cells respond to specific oncogenes. Cutaneous melanoma arises throughout the body, whereas the acral subtype arises on the palms of the hands, soles of the feet, or under the nails. We sequenced the DNA of cutaneous and acral melanomas from a large cohort of human patients and found a specific enrichment for BRAF mutations in cutaneous melanoma but CRKL amplifications in acral melanoma. We modeled these changes in transgenic zebrafish models and found that CRKL-driven tumors predominantly formed in the fins of the fish. The fins are the evolutionary precursors to tetrapod limbs, indicating that melanocytes in these acral locations may be uniquely susceptible to CRKL. RNA profiling of these fin/limb melanocytes, compared to body melanocytes, revealed a positional identity gene program typified by posterior HOX13 genes. This positional gene program synergized with CRKL to drive tumors at acral sites. Abrogation of this CRKL-driven program eliminated the anatomic specificity of acral melanoma. These data suggest that the anatomic position of the cell of origin endows it with a unique transcriptional state that makes it susceptible to only certain oncogenic insults.
Project description:Background:Physical forces, such as mechanical stress, are essential for tissue homeostasis and influence geneexpression of cells. In particular, the fibroblast has demonstrated sensitivity to extracellular matrices with assumedadaptation upon various mechanical loads. The purpose of this study was to compare the vocal fold fibroblastgenotype, known for its unique mechanically stressful tissue environment, with cellular counterparts at various otheranatomic locales to identify differences in functional gene expression profiles. Results:By using RNA-seq technology, we identified differentially expressed gene programs (DEseq2) among sevennormal human fibroblast primary cell lines from healthy cadavers, which included: vocal fold, trachea, lung, abdomen,scalp, upper gingiva, and soft palate. Unsupervised gene expression analysis yielded 6216 genes differentially expressedacross all anatomic sites. Hierarchical cluster analysis revealed grouping based on anatomic site origin rather thandonor, suggesting global fibroblast phenotype heterogeneity. Sex and age-related effects were negligible. Functionalenrichment analyses based on separate post-hoc 2-group comparisons revealed several functional themes within thevocal fold fibroblast related to transcription factors for signaling pathways regulating pluripotency of stem cells andextracellular matrix components such as cell signaling, migration, proliferation, and differentiation potential. Conclusions:Human fibroblasts display a phenomenon of global topographic differentiation, which is maintained inisolation via in vitro assays. Epigenetic mechanical influences on vocal fold tissue may play a role in uniquely modellingand maintaining the local environmental cellular niche during homeostasis with vocal fold fibroblasts distinctlyspecialized related to their anatomic positional and developmental origins established during embryogenesis.
Project description:Gene expression profiling of immortalized human mesenchymal stem cells with hTERT/E6/E7 transfected MSCs. hTERT may change gene expression in MSCs. Goal was to determine the gene expressions of immortalized MSCs.
Project description:Transcriptional profiling of human mesenchymal stem cells comparing normoxic MSCs cells with hypoxic MSCs cells. Hypoxia may inhibit senescence of MSCs during expansion. Goal was to determine the effects of hypoxia on global MSCs gene expression.