Hox genes and mesenchymal stem cells

We hypothesised that Hox proteins may play a role in the establishment of regional differences between different MSC isolates. The first step in understanding the potential function and regulation of Hox genes in MSC is to establish their exact expression patterns. We have mapped Hox gene expression in MSC from different sites of the body. The resulting expression profiles could then be compared to their anatomical origin and their differentiation potential. This showed that Hox genes in MSC are expressed in region specific patterns (Chapter 2). Having established the expression patterns for all Hox genes in the MSC, we attempted to identify the responsible regulatory elements. These elements may be located either outside of or within the Hox clusters. By expressing differently sized Hox constructs we have narrowed down some regions that might play a role in activation and regulation of Hox gene expression in MSC (Chapter 3). In a parallel approach, we have attempted to identify enhancer elements responsible for Hox gene expression in hematopoietic cells. Hox proteins play an important role in proliferation and differentiation of a variety of hematopoietic lineages. We showed that the elements that are responsible for expression of HOXA genes in hematopoietic cells are most likely located at a remote position outside the cluster. Also we developed an assay, which could potentially lead to the identification of these elusive elements (Chapter 4)