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In vivo haematopoietic activity is induced in neurosphere cells by chromatin‐modifying agents
Author(s) -
Schmittwolf Carolin,
Kirchhof Nicole,
Jauch Anna,
Dürr Michael,
Harder Friedrich,
Zenke Martin,
Müller Albrecht M
Publication year - 2005
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/sj.emboj.7600546
Subject(s) - biology , haematopoiesis , in vivo , chromatin , neurosphere , microbiology and biotechnology , cancer research , stem cell , in vitro , immunology , genetics , gene , endothelial stem cell , adult stem cell
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.