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Transcriptome analysis of human hepatic and pancreatic stellate cells: organ-specific variations of a common transcriptional phenotype

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Abstract

Pancreatic stellate cells (PSCs) are thought to be the primary source of the extensive fibrotic reaction characteristic of pancreatic cancer and chronic pancreatitis in humans. PSCs share many morphological and functional characteristics with hepatic stellate cells (HSCs), whose central role in liver fibrosis is well established. However, it has remained unclear if hepatic and pancreatic stellate cells are derived from a common cell lineage and if they are completely similar or if they possess organ-specific features. We have analysed the transcriptomes of HSCs, PSCs and skin fibroblasts to assess how the transcriptional phenotype of stellate cells differs from that of a typical fibroblast lineage cell and if there is evidence for a common stellate cell precursor. To this end, we have performed expression profiling of primary cultures of human HSCs, PSCs and skin fibroblasts using 23,000-feature ‘whole genome’ oligonucleotide micro-arrays. Expression data were verified using real-time PCR. The expression profiles of HSCs and PSCs displayed a great extent of similarity, clearly separating them from the fibroblasts. Predominantly extracellular and cell surface genes, but also signalling molecules, transcription factors and novel neural markers, were concordantly expressed in both stellate cell types. Despite this high degree of similarity, distinct differences in expression patterns were observed between HSCs and PSCs, reflecting organ-specific variations of the common stellate cell-specific phenotype.

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Acknowledgements

We thank S. Braun, C. Ruhland, K. Lanz and M. de Groot for excellent technical assistance. We are indebted to Dr. Kaufman, Department of Human Genetics, University of Ulm, for providing the short-term cultures of human skin fibroblasts. This work was supported by grants of the DFG to T.M.G. and M.B. (SFB 518, projects B1 and C4) and M.G.B. (SFB 518, project A7) and of the European Union to T.M.G. (QLG1-CT-2002-01196).

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Authors and Affiliations

  1. Department of Internal Medicine I, University Hospital of Ulm, 89081, Ulm, Germany

    Malte Buchholz, Hans A. Kestler, Karlheinz Holzmann, Volker Ellenrieder, Guido Adler, Thomas M. Gress & Thomas M. Gress

  2. Stiftungsdozentur Bioinformatik, University of Ulm, 89081, Ulm, Germany

    Hans A. Kestler

  3. Department of Clinical Chemistry, University Hospital of Ulm, 89081, Ulm, Germany

    Wilhelm Schneiderhan & Max G. Bachem

  4. Department of General, Visceral and Vascular Surgery, Ostalb-Klinikum, Aalen, Germany

    Marco Siech

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  1. Malte Buchholz
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  2. Hans A. Kestler
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  4. Volker Ellenrieder
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  7. Guido Adler
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  8. Max G. Bachem
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  9. Thomas M. Gress
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Correspondence to Thomas M. Gress.

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M. Buchholz and H. A. Kestler made equal contributions to this study and should both be considered first authors

M. G. Bachem and T. M. Gress made equal contributions to this study and should both be considered senior authors

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Buchholz, M., Kestler, H.A., Holzmann, K. et al. Transcriptome analysis of human hepatic and pancreatic stellate cells: organ-specific variations of a common transcriptional phenotype. J Mol Med 83, 795–805 (2005). https://doi.org/10.1007/s00109-005-0680-2

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  • DOI: https://doi.org/10.1007/s00109-005-0680-2

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