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First published online August 26, 2004
doi: 10.1242/10.1242/jcs.01291

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TGFß/BMP activate the smooth muscle/bone differentiation programs in mesoangioblasts

Enrico Tagliafico^1,*, Silvia Brunelli^2,*, Anna Bergamaschi¹, Luciana De Angelis^3,4, Raffaella Scardigli^3,4, Daniela Galli², Renata Battini¹, Paolo Bianco^3,5, Sergio Ferrari¹, Giulio Cossu^2,3,4, and Stefano Ferrari^1,

¹ Dipartimento di Scienze Biomediche, Università di Modena e Reggio Emilia, Via G. Campi 287, 41100 Modena, Italy
² Stem Cell Research Institute, Dibit, H. San Raffaele, Via Olgettina 58, 20132 Milano, Italy
³ Institute of Cell Biology and Tissue Engineering, San Raffaele Science Park, Via Castel Romano 100, 00128 Roma, Italy
⁴ Dipartimento di Istologia ed Embriologia, Università di Roma `La Sapienza', Via A. Scarpa 14, 00161 Roma, Italy
<sup>5</sup> Dipartimento di Medicina Sperimentale, Università di Roma `La Sapienza', Via A. Scarpa 14, 00161 Roma, Italy

Authors for correspondence (e-mail: ferrari.stefano{at}unimore.it; cossu.giulio{at}hsr.it)

Accepted 23 April 2004

Mesoangioblasts are vessel-derived stem cells that can be induced to differentiate into different cell types of the mesoderm such as muscle and bone. The gene expression profile of four clonal derived lines of mesoangioblasts was determined by DNA micro-array analysis: it was similar in the four lines but different from 10T1/2 embryonic fibroblasts, used as comparison. Many known genes expressed by mesoangioblasts belong to response pathways to developmental signalling molecules, such as Wnt or TGFß/BMP. Interestingly, mesoangioblasts express receptors of the TGFß/BMP family and several Smads and, accordingly, differentiate very efficiently into smooth muscle cells in response to TGFß and into osteoblasts in response to BMP. In addition, insulin signalling promotes adipogenic differentiation, possibly through the activation of IGF-R. Several Wnts and Frizzled, Dishevelled and Tcfs are expressed, suggesting the existence of an autocrine loop for proliferation and indeed, forced expression of Frzb-1 inhibits cell division. Mesoangioblasts also express many neuro-ectodermal genes and yet undergo only abortive neurogenesis, even after forced expression of neurogenin 1 or 2, MASH or NeuroD. Finally, mesoangioblasts express several pro-inflammatory genes, cytokines and cytokine receptors, which may explain their ability to be recruited by tissue inflammation. Our data define a unique phenotype for mesoangioblasts, explain several of their biological features and set the basis for future functional studies on the role of these cells in tissue histogenesis and repair.

Key words: Stem cells, DNA microarray, Differentiation

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