2011 - 2014
Dates of Study: Oct 2011 - Sept 2014
Programme: MRC PhD Programme in Stem Cell Biology
PhD Supervisor: Dr Bertie Göttgens
Studentship Sponsor: The Medical Research Council
Thesis Title: Decoding transcriptional networks in haematopoiesis using single cell gene expression analysis
From September 2014, Vicki began her PostDoc career in the lab of Dr Bertie Gottgens, at The Cambridge Instutute for Medical Research (CIMR) at The University of Cambridge.
Legend: Principal component analysis of 18 transcription factors in 597 primary bone marrow cells separates cells according to the cell type of origin. Green, HSC; Blue, LMPP; Purple, CLP; Red, GMP; Orange, PreMegE.
Legend: A regulatory triad predicted from correlation analysis of gene expression in single bone marrow stem and progenitor cells was validated experimentally. Gfi1 and Gfi1b are mutually inhibitory, while Gata2 can activate expression of Gfi1b, and Gfi1 can repress expression of Gata2.
Legend: 48 genes were measured in nearly 4000 single cells from 4 distinct anatomical stages during the development of blood in the mouse embryo. Hierarchical clustering identified three major clusters based on gene expression: I, early mesodermal cells; II, haemogenic endothelium; III, early blood cells. Coloured bar indicates embryonic stage of origin. Blue, primitive streak; green, neural plate; orange, head fold; red, 4 somite Runx1-GFP+; purple, 4 somite, Flk1+ Runx1-GFP-.
My PhD project has been interested in understanding how transcription factors regulate cell fate in the haematopoietic system. Much of what we know about transcription factors comes from population studies, but cell fate decisions are made at the level of individual cells. I have therefore been interested in using single cell gene expression analysis to understand the structure and function of transcriptional networks at the single cell level in adult haematopoiesis and during blood development in the embryo.
- Establishing the stem cell state: insights from regulatory network analysis of blood stem cell development (2012) Wiley Interdiscip Rev Syst Biol Med.
- Characterization of transcriptional networks in blood stem and progenitor cells using high-throughput single-cell gene expression analysis(2013) Nat Cell Biol.
- Transcriptional hierarchies regulating early blood cell development(2013). Blood Cells Mol Dis.
- Generation of multipotent foregut stem cells from human pluripotent stem cells (2013). Stem Cell Reports.
- Early dynamic fate changes in haemogenic endothelium characterized at the single-cell level (2013). Nat Commun.
- Transcriptional mechanisms of cell fate decisions revealed by single cell expression profilin (2014). Bioessays.
- Probabilistic PCA of censored data: accounting for uncertainties in the visualization of high-throughput single-cell qPCR data (2014). Bioinformatics.
- Key regulators control distinct transcriptional programmes in blood progenitor and mast cells (2014). EMBO J.
- Single-cell RNA sequencing reveals T helper cells synthesizing steroids de novo to contribute to immune homeostasis (2014). Cell Rep.