B. Hendrich Portrait

Dr Brian Hendrich

Transcriptional Control of Stem Cell Fate

Email: brian.hendrich@cscr.cam.ac.uk

Laboratory Location:

Wellcome Trust -  Medical Research Council Stem Cell Institute,  Hendrich Lab Members

Departmental Affiliation:

Department of Biochemistry, University of Cambridge

Co-workers:

María Barreira-GonzalezThomas BurgoldJulie CramardPedro Da SilvaRobin FloydSarah GharbiAnzy MillerMeryem Rasler Nicola Reynolds

Personal Information

Brian grew up near Seattle, Washington, and consequently is a consummate coffee snob.

Professional History


He got his PhD from Stanford University in 1995 working on X chromosome inactivation with Huntington Willard. In 1995 he joined the lab of Adrian Bird at the University of Edinburgh and participated in the discovery and characterisation of a family of methyl-CpG binding proteins in mammals.

In 2001 he obtained a Wellcome Trust Career Development Fellowship to start his own laboratory at the Institute for Stem Cell Research, University of Edinburgh. In 2008 he moved to the Wellcome Trust Centre for Stem Cell Research in Cambridge.

He is currently a Wellcome Trust Senior Research Fellow in the Basic Biomedical Sciences, and Director of the PhD Programme in Stem Cell Biology and Medicine for the Wellcome Trust - Medical Research Council Cambridge Stem Cell Institute.


 

Introduction

Embryonic stem (ES) cells hold enormous promise for personalised medicine and drug discovery since they can be maintained indefinitely and are pluripotent; that is they have the potential to form any adult cell type. While pluripotency makes ES cells potentially very useful, it also presents a problem: how do you get them to make the cell type you want, and not one you don't? Differentiation of pluripotent cells is exquisitely organised during normal embryogenesis, but controlling differentiation of stem cells in culture presents a major challenge. Since all cells in an organism are genetically identical, the observable differences in their functions and behaviours come down to which genes they express and which genes they don’t express. Therefore in order to understand how to direct cellular identity, we seek to understand how cells regulate gene expression during differentiation. We also seek to understand how subtle differences in gene expression patterns in seemingly identical cells influence any subsequent differentiation decisions. To do this we focus on how the DNA is packaged in the cell and study the proteins involved in regulating this chromatin packaging. We use biochemistry, genetics, in vitro stem cell culture and manipulation, single cell analyses, genome-wide analyses and collaborate with bioinformaticians and computer programmers to better understand how control of transcription facilitates decision making in stem cells. By understanding how ES cells make different developmental decisions this work will bring the medical promise of stem cells closer to realisation.

Image 1

Multiprotein transcriptional ‘corepressor’ complexes (top left) associate with DNA and, rather than simply turning off genes, act to modulate gene expression. Thus rather than acting in a binary fashion, these chromatin modifying protein activities can fine tune expression levels up or down. This activity allows cells to appropriately respond to developmental cues. Image: Brian Hendrich

 

Lab Information

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 they 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"

 

 

Follow us on Twitter: @BDH_Lab

 

 
 

 Click on the button above to see a morula turn into a blastocyst!
 (Video Credit Aoife O'Shaughnessy-Kirwan)

 

Lab Retreat 2014 Arthurs Seat

Lab retreat to Edinburgh August 2014

PHOTO CREDIT: Anzy Miller and her Troupe of ScienceArtists

Anzy's Cells

ES cells can self-renew, i.e. make new copies of themselves, or differentiate.

Cells

ES cells displaying heterogeneity for Klf4 protein (green) and counterstained with DAPI (blue)

Heatmap

Comparison of ChIP-Seq datasets in ES cells

(Lila Diamanti and Sabine Dietmann)

Postdoctoral Researchers

Keisuke Kaji 2002-2007 Currently: ESF Research Fellow, University of Edinburgh

Patrick McDonel 2007-2011 Currently: Postdoctoral Researcher, The Whitehead Institute, MIT

Dziugas Gineitis 2007-2009 Currently: Research Scientist (Industry, UK)

Paulina Latos 2008-2011 Currently: Postdoctoral Researcher, The Babraham Institute

Erin Knock 2009-2012 Currently: Postdoctoral Researcher, University of Toronto

Postgraduate Students

.  Jason Signolet, Wellcome Trust/MRC Four Year PhD Student, University of Cambridge, PhD Awarded 2014. Currently: Data Analyist and Koala Impersonator, Adelaide

.   Aoife O'Shaughnessy, BBSRC Case Studentship with Pfizer PLC, University of Cambridge, PhD Awarded 2012. Currently: Postgraduate Student, University of Cardiff AND Postdoctoral Scientist, Talisman Therapeutics Limited

.    Ita Costello, Wellcome Trust Four Year PhD Student, University of Edinburgh, PhD Awarded 2008. Currently: Postdoctoral Research Fellow, University of Oxford

.    Christine Powell (Heliwell), MRC PhD Studentship, University of Edinburgh, PhD Awarded 2007. Currently: Administrator, University of Edinburgh

.    Isabel Martin Caballero, School of Biological Sciences PhD Studentship, University of Edinburgh, PhD Awarded 2006. Currently: Postdoctoral Fellow, Karolinska Instituet

.    Lars Hansen, Masters Student from Raboud University Nijmegen, 2011-2012. Currently: PhD student, Oxford University

.    Philip Brennecke, Erasmus visiting Masters Student from Freie Universität, Berlin. 2008-2009. Currently: Postdoctoral Fellow, Stanford University.

.    Manoe Janssen, Erasmus visiting Masters Student from Raboud University Nijmegen, 2008. Currently: Postdoctoral Fellow K.U. Leuven, Belgium

Plain English

Embryonic stem cells can either make more copies of themselves, or differentiate to form any cell type in the body. How cells make the decision to differentiate, and which cell type to differentiate into, is controlled by gene expression patterns. We are studying how precise control of gene expression allows cells to make these decisions.

Key Publications

2Cell_Chd4

2 cell mouse embyro stained for Chd4 (white).

Embryos

Wild type (top) and Sin3a-null embryos stained for Eomes (green), Oct4 (blue) and Gata6 (red)

Morula

Morula stage embryo stained for Mi2beta

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