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  • The EMBO Journal (2005) 24, 554 - 566
  • doi:10.1038/sj.emboj.7600546

Published online: 20 January 2005

In vivo haematopoietic activity is induced in neurosphere cells by chromatin-modifying agents

Carolin Schmittwolf1,a, Nicole Kirchhof1,a, Anna Jauch2, Michael Dürr1, Friedrich Harder1, Martin Zenke3 and Albrecht M Müller1

  1. Institut für Medizinische Strahlenkunde und Zellforschung (MSZ), University of Würzburg, Würzburg, Germany
  2. Institut für Humanmedizin, Universität Heidelberg, Heidelberg, Germany
  3. Institute for Biomedical Engineering, Cell Biology, Aachen, Germany

Correspondence to:

Albrecht M Müller, Institut für Medizinische Strahlenkunde und Zellforschung (MSZ), University of Würzburg, Versbacherstr. 5, 97078 Würzburg, Germany. Tel.: +49 931 201 45848; Fax: +49 931 201 45147; E-mail: albrecht.mueller@mail.uni-wuerzburg.de

aThese authors contributed equally to this work

Received 27 May 2004; Accepted 14 December 2004

Modifications of DNA and chromatin are fundamental for the establishment and maintenance of cell type-specific gene expression patterns that constitute cellular identities. To test whether the developmental potential of fetal brain-derived cells that form floating sphere colonies (neurospheres) can be modified by destabilizing their epigenotype, neurosphere cells were treated with chemical compounds that alter the acetylation and methylation patterns of chromatin and DNA. Intravenous infusion of bulk or clonally derived neurosphere cells treated with a combination of trichostatin A (TSA) plus 5-aza-2'-deoxycytidine (AzaC) (TSA/AzaC neurosphere cells) yielded long-term, multilineage and transplantable neurosphere-derived haematopoietic repopulation. Untreated neurosphere cells exhibited no haematopoietic repopulation activity. The neurosphere-derived haematopoietic cells showed a diploid karyotype, indicating that they are unlikely to be products of cell fusion events, a conclusion strengthened by multicolour fluorescence in situ hybridization. Our results indicate that altering the epigenotype of neurosphere cells followed by transplantation enables the generation of neurosphere-derived haematopoietic cells.

  • Keywords:

    • chromatin-modifying agents,
    • developmental potential of neurosphere cells,
    • haematopoietic activity of neurospheres,
    • trichostatin A,
    • 5-Aza-2'-dC