Ectopic expression of CDX4 in human mesenchymal stem cells does not affect HOX gene expression or induce hematopoietic reprogramming.
In vitro generation of large numbers of autologous hematopoietic stem cells would be extremely useful for clinical applications. Adipose tissue derived mesenchymal stem cells (AT-MSC) are an easily available autologous source for cell therapy applications. Like hematopoietic cells, MSC are of mesodermal origin. The Cdx-Hox pathway is an important genetic program for hematopoiesis, where Cdx4 is a key upstream regulator of the Hox family. We introduced ectopic CDX4 gene in an attempt to reprogram AT-MSC to differentiate along the hematopoietic lineage. To further promote hematopoietic reprogramming, we cultured the transduced cells in cocktails of hematopoietic cytokines, growth factors or epigenetic modifiers. However, despite strong expression of CDX4 at the mRNA and protein levels, neither downstream HOX genes, other genes of importance for hematopoietic development or functional colony forming assays showed any evidence of hematopoietic reprogramming. Thus, despite the close developmental association between these cell types, the introduction of one single master switch transcription factor was not sufficient to promote hematopoietic reprogramming in AT-MSC.
Institute of Immunology and Norwegian Center for Stem Cell Research, Oslo University Hospital; Rikshospitalet and Institute of Basic Medical Sciences, University of Oslo, P.O. Box 1121 Blindern, 0317 Oslo, Norway. Krisztina.Szoke@rr-research.no
Krisztina
K
Szöke
Karen Johanne
KJ
Beckstrøm
Jan E
JE
Brinchmann
D000293:Adolescent; D000328:Adult; D055415:Bone Morphogenetic Protein 4 / Q000494:pharmacology; D048430:Cell Shape / Q000187:drug effects; D065150:Cellular Reprogramming / Q000187:drug effects / Q000235:genetics*; D003114:Colony-Forming Units Assay; D016207:Cytokines / Q000494:pharmacology; D044127:Epigenesis, Genetic / Q000187:drug effects; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000187:drug effects*; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006410:Hematopoiesis / Q000187:drug effects / Q000235:genetics*; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D012190:Retroviridae / Q000235:genetics; D014161:Transduction, Genetic; D055815:Young Adult
D055415:Bone Morphogenetic Protein 4; C579354:CDX4 protein, human; D016207:Cytokines; D018398:Homeodomain Proteins; D049452:Green Fluorescent Proteins