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Brian Hendrich

Transcriptional control of stem cell fate

Cells of early mammalian embryos have the potential to develop into any adult cell type, and are thus said to be pluripotent. Pluripotency is lost during embryogenesis as cells begin to commit to specific developmental pathways.

The goal of the group is to understand the transcriptional regulatory mechanisms that underpin the ability of a homogeneous population of pluripotent cells to give rise to the massive heterogeneity existing in somatic tissues. To achieve this we are using a combination of biochemistry, genetics, developmental biology, bioinformatics, ES cell manipulation, in vitro differentiation, proteomics, and gene expression analyses.

 

We are part of the EU FP7 Project "4DCellFate"

We are part of the Marie Curie Initial Training Network "DisChrom"

 

Lab members: Maria Barreira-Gonzalez, Thomas Burgold, Robin Floyd, Sarah Gharbi, Anzy Miller, Aoife O'Shaugnessy-Kirwan, Meryem Rasler, Nicola Reynolds, Jason Signolet

Visit group website at the Stem Cell Institute

Key publications:

1. dos Santos, R., Tosti, L., Radzisheuskaya, A., Caballero, I.M., Kaji, K*., Hendrich, B*. and Silva, J.C.R. * (2014) Mbd3/NuRD facilitates induction of pluripotency in a context dependent manner Cell Stem Cell doi: 10.1016/j.stem.2014.04.019 *co-senior authors

2. O’Shaughnessy, A. and Hendrich, B. (2013) CHD4 in the DNA-damage response and cell-cycle progression: not so NuRDY now. Biochem. Soc. Trans. 41(3):777-782. doi:10.1042/BST20130027.

3. Reynolds, N., O’Shaughnessy, A. and Hendrich, B. (2013) "Transcriptional repressors: multifaceted regulators of gene expression" Development, 140(3), 505–512. doi:10.1242/dev.083105

4. Reynolds, N., Latos, P., Hynes-Allen, A., Loos, R., Leaford, D., O’Shaughnessy, A., Mosaku, O., Signolet, J., Brennecke, P., Kalkan, T., Costello, I., Humphreys, P., Mansfield, W., Nakagawa, K., Strouboulis, J., Behrens, A. Bertone, P., and Hendrich, B. (2012) “NuRD suppresses pluripotency gene expression to promote transcriptional heterogeneity and lineage commitment”  Cell Stem Cell 10(5): 583-594. 10.1016/j.stem.2012.02.020 Open access: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3402183/

5. Latos, P.A., Helliwell, C., Mosaku, O., Dudzinska, D.A., Stubbs, B.,Berdasco, M., Esteller, M., Hendrich, B. (2012) NuRD-dependent DNA methylation prevents ES cells from accessing a trophectoderm fate. Biology Open

6. McDonel, P., Demmers, J., Tan, D.M.W., Watt, F., and Hendrich, B. (2012) “Sin3a is essential for the genome integrity and viability of pluripotent cells.” Developmental Biology 363:62, doi:10.1016/j.ydbio.2011.12.019

7. Reynolds, N., Salmon-Divon, M., Dvinge, H., Balasooriya, G., Leaford, D., Hynes-Allen, A., Behrens, A., Bertone, P. and Hendrich, B. (2012) “NuRD-mediated deacetylation of H3K27 facilitates recruitment of Polycomb Repressive Complex 2 to direct gene repression” EMBO Journal 31:593, doi:10.1038/emboj.2011.431