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.

► The Cdx-Hox pathway is important in hematopoiesis.
► Cdx4 is upstream regulator of the Hox family.
► Ectopic expression of the CDX4 gene did not affect HOX gene expression in AT-MSC.
► The master switch CDX4 alone did not promote hematopoietic reprogramming in AT-MSC.