Research themes: Stem cells, leukaemia, single cell biology, microfluidics, physical biology
Group members: Miriam Belmonte, Daniel Bode, James Che, Craig McDonald, Nina Oebro, Caroline Oedekoven, Sandra Pietsch, Juan Rubio, Mairi Shepherd
Description of research
One of the simplest and most provocative concepts in all of stem cell biology is how a single stem cell can give rise to both copies of itself as well as daughter cells that can give rise to any of the highly specialized cell types of a given tissue. As a population, this decision making process must exist in a tightly regulated balance in order to avoid tissue degeneration (too few stem cells) or progression to cancer (too many stem cells). Many malignancies are thought to arise from a mutation or series of mutations in a single stem cell that goes on to cause an overproduction of cells eventually leading to cancer. Our lab focuses on how aberrant cell fate choice drives malignancy on a single cell level.
Our current research is focused on three main themes in adult blood stem cell biology:
1) Molecular drivers of blood stem cell heterogeneity
2) The early stages of cancer evolution from single cells
3) Blood stem cell expansion outside the body
The Kent lab is grateful for research funding from Bloodwise, the European Research Council, the European Hematology Association and the Rosetrees Trust. Students and postdocs have received funding from the Wellcome Trust, BBSRC, MRC and Danish Lundbeck Foundation.
Figure caption: A small colony of cells derived from a single blood stem cell. Hundreds of such colonies can be assessed for their proliferation kinetics and blood cell types produced.
- Nestorowa S, Hamey FK, Pijuan Sala B, Diamanti E, Shepherd M, Laurenti E, Wilson NK, *Kent DG, *Göttgens B. A single cell resolution map of mouse haematopoietic stem and progenitor cell differentiation Blood. 2016 Jun 30. pii: blood-2016-05-716480.
- Schulte R, Wilson NK, Prick JC, Cossetti C, Maj MK, Gottgens B, Kent DG. Index sorting resolves heterogeneous murine hematopoietic stem cell populations. Exp Hematol. 2015 Sep;43(9):803-11.
- *Wilson NK, *Kent DG, Buettner F. Combined Single-Cell Functional and Gene Expression Analysis Resolves Heterogeneity within Stem Cell Populations. Cell Stem Cell. 2015 June Jun 4;16(6):712-24.
- Ortmann CA, *Kent DG, Nangalia J, Silber Y, Wedge DC, Grinfeld J, Baxter EJ, Massie CE, Papaemmanuil E, Menon S, Godfrey AL, Dimitropoulou D, Guglielmelli P, Bellosillo B, Besses C, Döhner K, Harrison CN, Vassiliou GS, Vannucchi A, Campbell PJ, Green AR. The Effect of Mutation Order on Myeloproliferative Neoplasms. N Eng J Med. 2015 Feb 12;372(7):601-612.
- Kent DG, Li J, Tanna H, Fink J, Kirschner K, Pask DC, Silber Y, Hamilton TL, Sneade R, Simons BD, Green AR. Self-renewal of single mouse hematopoietic stem cells is reduced by JAK2V617F without compromising progenitor cell expansion. PLoS Biol. 2013;11(6):e1001576.
- Kent DG, Copley MR, Benz C, Wöhrer S, Dykstra BJ, Ma E, Cheyne J, Zhao Y, Bowie MB, Zhao Y, Gasparetto M, Delaney A, Smith C, Marra M, Eaves CJ. Prospective isolation and molecular characterization of hematopoietic stem cells with durable self-renewal potential. Blood. 2009 Jun 18;113(25):6342-50.
- Kent DG, Dykstra BJ, Cheyne J, Ma E, Eaves CJ. Steel factor coordinately regulates the molecular signature and biologic function of hematopoietic stem cells. Blood. 2008 Aug 1;112(3):560-7.
- Dykstra B, Kent D, Bowie M, McCaffrey L, Hamilton M, Lyons K, Lee SJ, Brinkman R, Eaves C. Long-term propagation of distinct hematopoietic differentiation programs in vivo. Cell Stem Cell. 2007 Aug 16;1(2):218-29.
- Kent DG, Green AR. Order Matters: The Order of Somatic Mutations Influences Cancer Evolution. Cold Spring Harb Perspect Med. 2017 Jan 17. pii: a027060.
- Prick J, de Haan G, Green AR, Kent DG. Clonal heterogeneity as a driver of disease variability in the evolution of myeloproliferative neoplasms. Exp Hematol. 2014 Oct;42(10):841-51.