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PMID: 15660132 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

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

The EMBO journal ·Vol. 24 ·No. 3 ·2005-02-09 ·Pages 554-66

Schmittwolf C, Kirchhof N, Jauch A, Dürr M, Harder F, Zenke M, Müller AM

Abstract

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.

MeSH Terms
Animals Azacitidine/analogs & derivatives,pharmacology Chromatin/drug effects Decitabine Diploidy Genes, bcl-2 Green Fluorescent Proteins/genetics Hematopoiesis/drug effects Hematopoietic Stem Cells/cytology,drug effects Humans Hydroxamic Acids/pharmacology In Vitro Techniques Karyotyping Mice Mice, Inbred C57BL Mice, Transgenic Multipotent Stem Cells/cytology,drug effects Neurons/cytology,drug effects Spheroids, Cellular
Chemicals
Chromatin Hydroxamic Acids enhanced green fluorescent protein Green Fluorescent Proteins trichostatin A Decitabine Azacitidine
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Schmittwolf Carolin
Institut für Medizinische Strahlenkunde und Zellforschung (MSZ), University of Würzburg, Würzburg, Germany.
Kirchhof Nicole
Jauch Anna
Dürr Michael
Harder Friedrich
Zenke Martin
Müller Albrecht M
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Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
DOI
10.1038/sj.emboj.7600546
Published
2005-02-09
Epub
2005-00-20
Pages
554-66
Language
English
Region
England
NLM ID
8208664
PMCID
PMC548653
Subset
IM
External Links
PubMed source DOI: 10.1038/sj.emboj.7600546 PMC Full Text View journal details
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