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      Tissue specific human fibroblast differential expression based on RNAsequencing analysis

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          Abstract

          Background

          Physical forces, such as mechanical stress, are essential for tissue homeostasis and influence gene expression of cells. In particular, the fibroblast has demonstrated sensitivity to extracellular matrices with assumed adaptation upon various mechanical loads. The purpose of this study was to compare the vocal fold fibroblast genotype, known for its unique mechanically stressful tissue environment, with cellular counterparts at various other anatomic locales to identify differences in functional gene expression profiles.

          Results

          By using RNA-seq technology, we identified differentially expressed gene programs (DEseq2) among seven normal 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 expressed across all anatomic sites. Hierarchical cluster analysis revealed grouping based on anatomic site origin rather than donor, suggesting global fibroblast phenotype heterogeneity. Sex and age-related effects were negligible. Functional enrichment analyses based on separate post-hoc 2-group comparisons revealed several functional themes within the vocal fold fibroblast related to transcription factors for signaling pathways regulating pluripotency of stem cells and extracellular matrix components such as cell signaling, migration, proliferation, and differentiation potential.

          Conclusions

          Human fibroblasts display a phenomenon of global topographic differentiation, which is maintained in isolation via in vitro assays. Epigenetic mechanical influences on vocal fold tissue may play a role in uniquely modelling and maintaining the local environmental cellular niche during homeostasis with vocal fold fibroblasts distinctly specialized related to their anatomic positional and developmental origins established during embryogenesis.

          Electronic supplementary material

          The online version of this article (10.1186/s12864-019-5682-5) contains supplementary material, which is available to authorized users.

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          Most cited references92

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          Hyaluronic acid (hyaluronan): a review

          Hyaluronic acid (HA) is a high molecular weight biopolysacharide, discovered in 1934, by Karl Meyer and his assistant, John Palmer in the vitreous of bovine eyes. Hyaluronic acid is a naturally occurring biopolymer, which has important biological functions in bacteria and higher animals including humans. It is found in most connective tissues and is particularly concentrated in synovial fluid, the vitreous fluid of the eye, umbilical cords and chicken combs. It is naturally synthesized by a class of integral membrane proteins called hyaluronan synthases, and degraded by a family of enzymes called hyaluronidases. This review describes metabolisms, different physiological and pathological functions, basic pharmacological properties, and the clinical use of hyaluronic acid.
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            Making or breaking the heart: from lineage determination to morphogenesis.

            The cues governing cardiac cell-fate decisions, cardiac differentiation, and three-dimensional morphogenesis are rapidly being elucidated. Several themes are emerging that are relevant for childhood and adult heart disease and the growing field of stem cell biology. This review will consider our current understanding of cardiac cell-fate determination and cardiogenesis--largely derived from developmental studies in model organisms and human genetic approaches--and examine future implications for diagnosis, prevention, and treatment of heart disease in the young and old.
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              The arterial pole of the mouse heart forms from Fgf10-expressing cells in pharyngeal mesoderm.

              Development of the arterial pole of the heart is a critical step in cardiogenesis, yet its embryological origin remains obscure. We have analyzed a transgenic mouse line in which beta-galactosidase activity is observed in the embryonic right ventricle and outflow tract of the heart and in contiguous splanchnic and pharyngeal mesoderm. The nlacZ transgene has integrated upstream of the fibroblast growth factor 10 (Fgf10) gene and comparison with the expression pattern of Fgf10 in pharyngeal mesoderm indicates transgene control by Fgf10 regulatory sequences. Dil labeling shows a progressive movement of cells from the pharyngeal arch region into the growing heart tube between embryonic days 8.25 and 10.5. These data suggest that arterial pole myocardium originates outside the classical heart field.
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                Author and article information

                Contributors
                thibeault@surgery.wisc.edu
                Journal
                BMC Genomics
                BMC Genomics
                BMC Genomics
                BioMed Central (London )
                1471-2164
                23 April 2019
                23 April 2019
                2019
                : 20
                : 308
                Affiliations
                [1 ]ISNI 0000 0001 0701 8607, GRID grid.28803.31, Department of Surgery, Division of Otolaryngology – Head and Neck Surgery, , University of Wisconsin, ; Madison, WI USA
                [2 ]ISNI 0000 0001 2167 3675, GRID grid.14003.36, Department of Statistics, , University of Wisconsin – Madison, College of Letters and Science, ; Madison, WI USA
                [3 ]ISNI 0000 0001 2167 3675, GRID grid.14003.36, Department of Biostatistics & Medical Informatics, , University of Wisconsin – Madison, ; Madison, WI USA
                Article
                5682
                10.1186/s12864-019-5682-5
                6480701
                31014251
                ca21f06d-672f-4428-ae1d-da3e3d9b6ede
                © The Author(s). 2019

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 21 August 2018
                : 9 April 2019
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/100000002, National Institutes of Health;
                Award ID: DC4336
                Funded by: FundRef http://dx.doi.org/10.13039/100000056, National Institute of Nursing Research;
                Award ID: dc9401
                Categories
                Research Article
                Custom metadata
                © The Author(s) 2019

                Genetics
                vocal fold biology,rna-seq,human vocal fold fibroblast,functional gene expression,transcriptome profiling,mechanobiology,mechanical force

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