The role of the homeobox gene Hesx1 in stem cell fate. (360G-Wellcome-096618_Z_11_A)

The elucidation of the transcriptional mechanisms underlying cell stemness is an important goal of modern cell biology and a vast amount of research has revealed the functionof several transcription factors in the maintenance and induction of pluripotency. Hesx1,encoding a transcriptional repressor, is a critical homeobox gene during normal vertebrate development and its absence leads toforebrain and pituitary defects in all species analysed, including humans. Despite the fact that Hesx1 was initially cloned from mouse ES cells 27 years ago, there is no information on its function in these cells. Preliminary research from the hostlab has shown that Hesx1-deficient ES cells have a similar molecular signature to epiblast stem cells (EpiSC), suggesting that HESX1 may beinvolved in the maintenance of ES versus Epi cellfates. In addition, Sara has identified from microarray data available in theliterature, that the core pluripotency factors SOX2, OCT4, Nanog and TCF3 are bound to the promoter region of Hesx1. Finally, we have preliminary data indicating that Hesx1 is expressed in the inner cell mass of the 3.5-4.5 days post coitum (dpc) mouse blastocyst. In addition she will identify HESX1 transcriptional targets in order to understand at the molecular level the function of HESX1 in these cells.