Tissue Engineering from Prominin-1/CD133+ stem and progenitor cells
Publications Grants Collaboration in Dresden Technology Platform Lecture materialsPrevious and current research
The focus of our research is to understand the first step of tissue formation, which relies on the cell biological basis of stem cell proliferation and differentiation. We particularly concentrate on stem cells that express the marker prominin-1 (CD133).
Fig. 1 - Membrane topology of prominin-1 (CD133).
Previously, we have reported the molecular and cell biological characterization of prominin-1, a pentaspan membrane glycoprotein (Fig. 1). This cholesterol-binding protein is specifically associated with plasma membrane protrusions, irrespective of the cell type, by a molecular mechanism that involves a membrane lipid microdomain. We have identified also a second prominin molecule (referred to as prominin-2) that exhibits a similar, but not identical, tissue distribution and subcellular localization to prominin-1. Moreover, several splice variants of prominin-1 have been identified and characterized. They show a broad range of expression, from myelin to the tail of spermatozoa. Importantly, prominin-1 is expressed in several stem cells originating from various sources, including the neural and hematopoietic system, and prominin-1 is now used for stem cell isolation. Likewise, certain epitopes, e.g. AC133, of prominin-1 might be used as markers of cancer stem cells.
The physiological function of these pentaspan membrane glycoproteins, which are conserved through metazoan evolution, remains to be established. Nevertheless, the general preference of these proteins for plasma membrane protrusions – including the membrane evaginations at the based of the outer segment of photoreceptor cells – and the identification of mutations in the human PROM-1 gene that cause retinal degeneration, have led to the hypothesis that prominin-1 acts as an organizer of plasma membrane protrusions.
Fig. 2 - Hematopoietic stem cells growing on multipotent mesenchymal stromal cells as feeder cell layer.
Future prospects and goals
In the future, we will functionally characterize prominins using molecular and cell biological approaches as well as animal models (mouse, zebrafish, axolotl). Besides studying the cell biological basis of tissue formation, in particular in the hematopoietic system (see Fig. 2 and Fig. 3), my lab will also investigate the cellular and molecular mechanisms underlying the retinal degeneration associated with mutations in the PROM-1 gene, and evaluate the possibility of using prominin-1 as a novel tool in the diagnosis of retinal degeneration.
Fig. 3 - Symmetric and asymmetric distribution of prominin-1 (AC133 epitope) in dividing hematopoietic stem cells (for details see Fargeas et al., (2006) Future Lipidology; Bauer et al., (2008) Cells Tissues Organs; Fonseca et al., (2008) Blood Cells Mol Dis). White arrows indicate the midbody. Bars, 5 µm.Finally, the role of prominins in lipid raft membrane microdomain formation will be investigated, as well as the function of these microdomains in normal prominin-1+ hematopoietic stem cells and their leukemic counterparts.
Selected Publications
Weigmann, A., D. Corbeil, A. Hellwig and W.B. Huttner. (1997) Prominin, a novel microvilli-specific polytopic membrane protein of the apical surface of epithelial cells, is targeted to plasmalemmal protrusions of nonepithelial cells. Proc. Natl. Acad. Sci. USA. 94: 12425-12430
Maw, M.A., D. Corbeil, J. Koch, A. Hellwig, J.C. Wilson-Wheeler, R.J. Bridges, G. Kumaramanickavel, S. John, D. Nacarrow, K. Röper, A. Weigmann, W.B. Huttner and M.J. Denton. (2000) A frameshift mutation in prominin (mouse)-like 1 causes human retinal degeneration. Hum. Mol. Genet. 9: 27-34
Röper, K., D. Corbeil and W.B. Huttner. (2000) Retention of prominin in microvilli reveals distinct cholesterol-based lipid microdomain within the apical membrane of epithelial cells. Nature Cell Biol. 2: 582-592
Fargeas, C.A., M. Florek, W.B. Huttner and D. Corbeil. (2003) Characterization of Prominin-2, a new member of the prominin family of pentaspan membrane glycoproteins. J. Biol. Chem. 278: 8586-8596
Lee, A., J.D. Kessler, T.-A. Read, C. Kaiser, D. Corbeil, W.B. Huttner, J.E. Johnson, R.J. Wechsler-Reya. (2005) Isolation of neural stem cells from postnatal cerebellum. Nature. Neurosci. 8: 715-719
Huttner, H.B., P. Janich, M. Köhrmann, J. Jászai, F. Siebzehnrubl, I. Blümcke, M. Suttorp, M. Gahr, D. Kuhnt, C. Nimsky, D. Krex, G. Schackert, K. Löwenbrück, H. Reichmann, E. Jüttler, W. Hacke, P. D. Schellinger, S. Schwab, M. Wilsch-Bräuninger, A.-M. Marzesco, and D. Corbeil. (2008) The stem cell marker prominin-1/CD133 on membrane particles in human cerebrospinal fluid offers novel approaches for studying CNS disease. Stem cells. 26: 698-705
Karbanová, J., E. Missol-Kolka, A.-V. Fonseca, C. Lorra, P. Janich, H. Hollerová, J. Jászai, J. Ehrmann, Z. Kolář, C. Liebers, S. Arl, D. Šubrtová, D. Freund, J. Mokrý, W.B. Huttner and D. Corbeil. (2008) The stem cell marker CD133 (Prominin-1) is expressed in various human glandular epithelia. J Histochem Cytochem. In Press
Nomenclature of Prominin Molecules
Fargeas, C.A., D. Corbeil§ and W.B. Huttner. (§corresponding author). (2003) AC133 antigen, CD133, prominin-1, prominin-2, Etc.: Prominin family gene products in need of a rational nomenclature. Stem Cells. 21: 506-508
Fargeas, C.A., W.B. Huttner and D. Corbeil. (2007) Nomenclature of prominin-1 (CD133) splice variants – An update. Tiss Antig. 69: 602-606
Reviews
Corbeil, D., K. Röper, C.A. Fargeas, A. Joester and W.B. Huttner. (2001) Prominin: A story of cholesterol, plasma membrane protrusions and human pathology. Traffic 2: 82-91
Fargeas, C.A., A.-V. Fonseca, W.B. Huttner and D. Corbeil. (2006) Prominin-1 (CD133) – from progenitor cells to human diseases. Future Lipidology. 1: 213-225
Jászai, J., C.A. Fargeas, M. Florek, W.B. Huttner and D. Corbeil. (2007) Focus on Molecules: Prominin-1 (CD133). Exp. Eye Res. 85: 585-586
Denis Corbeil
1994: Ph.D. University
of Montreal, Canada
1994-1997: Postdoctoral
work at the Department of
Neurobiology, University
of Heidelberg
1997-2001: Staff Scientist
at the Department of Neurobiology,
University of Heidelberg
2001-2004: Group Leader at
Medical Clinic and Polyclinic I
of TU Dresden
with joint appointment at MPI-CBG
2004-present: Group Leader at
Biotechnology Center of the TU Dresden
Contact:
Dr. Denis Corbeil
Tissue Engineering Laboratories
Biotechnology Center (BIOTEC)
Technische Universität Dresden
Tatzberg 47-51
01307 Dresden, Germany
Phone: +49 351 463 40118
E-mail: denis.corbeil(at)biotec.tu-dresden.de
City and University Information
Dresden
Technische Universität Dresden (TUD)
