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Molecular and Cellular Biology, November 2005, p. 9509-9519, Vol. 25, No. 21
0270-7306/05/$08.00+0     doi:10.1128/MCB.25.21.9509-9519.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Activation of Myogenic Differentiation Pathways in Adult Bone Marrow-Derived Stem Cells{dagger}

Fikru Belema Bedada,1 Antje Technau,2 Henning Ebelt,2,3 Manja Schulze,1,2 and Thomas Braun1*

Max Planck Institute for Heart and Lung Research, Parkstr. 1, 61231 Bad Nauheim, Germany,1 Institute of Physiological Chemistry, University of Halle, Halle, Germany,2 Department of Medicine III, University of Halle, Halle, Germany3

Received 1 May 2005/ Returned for modification 28 May 2005/ Accepted 20 August 2005

During embryogenesis, various cell types can be programmed by potent inducers to follow distinct differentiation paths. In adult life, this ability seems to be restricted to specific multipotent cells. We have identified two cell populations from adult murine bone marrow which express various "stemness" genes. Treatment with Wnt molecules induced transcription of different skeletal muscle marker genes and evoked expression of cardiomyocyte markers. Further characterization of Wnt-induced intracellular signaling cascades revealed that the skeletal muscle program depended on canonical Wnt signaling, while the induction of cardiomyocyte markers seems to require a protein kinase C-dependent pathway. CDO, another component of the machinery directing skeletal muscle induction and expansion, selectively activated skeletal muscle- but not cardiomyocyte-specific genes. Although we were able to turn on various cell-type-specific markers by different induction regimens, we never obtained fully differentiated, functional cells. We conclude that the differentiation of adult stem cells is incomplete and lacks certain cues necessary to acquire a truly functional status.


* Corresponding author. Mailing address: Max Planck Institute for Heart and Lung Research, Parkstr. 1, 61231 Bad Nauheim, Germany. Phone: 49-0-6032-705-401. Fax: 49-0-6032-705-419. E-mail: thomas.braun{at}kerckhoff.mpg.de.

{dagger} Supplemental material for this article may be found at http://mcb.asm.org/.


Molecular and Cellular Biology, November 2005, p. 9509-9519, Vol. 25, No. 21
0022-538X/05/$08.00+0     doi:10.1128/MCB.25.21.9509-9519.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.




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