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Global gene expression analyses of hematopoietic stem cell-like cell lines with inducible Lhx2 expression

Richter, Karin (författare)
Umeå universitet,Umeå centrum för molekylär medicin (UCMM)
Wirta, Valtteri (författare)
Dahl, Lina, 1981- (författare)
Umeå universitet,Umeå centrum för molekylär medicin (UCMM)
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Bruce, Sara (författare)
Karolinska Institutet
Lundeberg, Joakim (författare)
Carlsson, Leif (författare)
Umeå universitet,Umeå centrum för molekylär medicin (UCMM)
Williams, Cecilia (författare)
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 (creator_code:org_t)
2006-04-06
2006
Engelska.
Ingår i: BMC Genomics. - : Springer Science and Business Media LLC. - 1471-2164. ; 7, s. 75-
  • Tidskriftsartikel (refereegranskat)
Abstract Ämnesord
Stäng  
  • Background Expression of the LIM-homeobox gene Lhx2 in murine hematopoietic cells allows for the generation of hematopoietic stem cell (HSC)-like cell lines. To address the molecular basis of Lhx2 function, we generated HSC-like cell lines where Lhx2 expression is regulated by a tet-on system and hence dependent on the presence of doxycyclin (dox). These cell lines efficiently down-regulate Lhx2 expression upon dox withdrawal leading to a rapid differentiation into various myeloid cell types. Results Global gene expression of these cell lines cultured in dox was compared to different time points after dox withdrawal using microarray technology. We identified 267 differentially expressed genes. The majority of the genes overlapping with HSC-specific databases were those down-regulated after turning off Lhx2 expression and a majority of the genes overlapping with those defined as late progenitor-specific genes were the up-regulated genes, suggesting that these cell lines represent a relevant model system for normal HSCs also at the level of global gene expression. Moreover, in situ hybridisations of several genes down-regulated after dox withdrawal showed overlapping expression patterns with Lhx2 in various tissues during embryonic development. Conclusion Global gene expression analysis of HSC-like cell lines with inducible Lhx2 expression has identified genes putatively linked to self-renewal / differentiation of HSCs, and function of Lhx2 in organ development and stem / progenitor cells of non-hematopoietic origin.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)

Nyckelord

Animals
Cell Differentiation
Down-Regulation
Doxycycline/metabolism/pharmacology
Embryo/cytology/metabolism
Gene Expression Regulation
Hematopoietic Stem Cells/drug effects/*metabolism
Homeodomain Proteins/genetics/*metabolism
In Situ Hybridization
Mice
Models; Biological
Oligonucleotide Array Sequence Analysis
Tetracycline/metabolism/pharmacology
Transcription Factors/genetics/*metabolism
Molecular medicine
Molekylär medicin
molecular medicine (medical sciences)
molekylär medicin (medicinska vetenskaper)

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