Dataset: FunGenES: UED-LF2: HOXB4 can enhance the differentiation of embryonic stem cells by modulating the haematopoietic niche

[u'This experiment is part of the FunGenES project (FunGenES - Functional Genomics in Embryonic Stem Cells partially funded by the 6th Framework Programme of the European Union, ', {u'a': {u'href': u'http://www.fungenes.org', u'target': u'_blank', u'$': u'http://www.fungenes.org'}}, u').The experiment was conducted at the MRC Centre for Regenerative Medicine, University of Edinburgh, UK. Aim of the experimet is to study the pro-haematopoietic effect of HOXB4 in differentiating ES cells. Haematopoietic differentiation of embryonic stem (ES) cells in vitro has been used as a model to study early haematopoietic development and it is well documented that haematopoietic differentiation can be enhanced by over-expression of HOXB4. HOXB4 is expressed in haematopoietic progenitor cells (HPC) where it promotes self-renewal, but it is also expressed in the primitive streak of the gastrulating embryo. This led us to hypothesise that HOXB4 might modulate gene expression in pre- haematopoietic mesoderm and that this property might contribute to its pro-haematopoietic effect in differentiating ES cells. To test our hypothesis we developed a conditionally activated HOXB4 expression system using the mutant oestrogen receptor (ERT2) and showed that a pulse of HOXB4 prior to HPC emergence in differentiating ES cells led to an increase in haematopoietic differentiation. Expression profiling revealed an increase in the expression of genes associated with paraxial mesoderm that gives rise to the haematopoietic niche. Cell mixing experiments suggest that HOXB4 activation can indeed have a paracrine, as well as a cell autonomous, effect on haematopoietic differentiation. We provide evidence that this may, in part, be mediated by modulation of the Wnt pathway via the HOXB4 target gene, Frzb.']

Species:

mouse

Samples:

18

Source:

E-MTAB-547

Updated:

Dec.12, 2014

Registered:

Nov.21, 2014