Profiling primitive haematopoietic progenitors in the vertebrate embryo

Thesis

The primitive wave of haematopoiesis provides an initial circulatory system used during vertebrate embryonic development. During the primitive wave, lateral plate mesoderm cells, expressing the transcription factor Scl, contribute to both blood and vasculature progenitors. Scl protein is required for the development of all blood lineages in zebrafish, while in mice Scl knockout results in prenatal fatalities due to complete absence of early haematopoiesis. The highly dynamic nature and small cell number of primitive haematopoietic progenitors have to date hindered in depth in vivo studies of this developmentally crucial population. Using genome-wide profiling of scl-expressing progenitors in zebrafish I have shown that early primitive haematopoietic programmes at the anterior and posterior of the embryos, are distinct at the level of both transcriptional and chromatin landscapes. I have identified characteristic anterior and posterior transcriptional signatures and associated putative cis-regulatory modules, correlating with divergent biological functions in these populations.

In particular, I have characterised the cellular heterogeneity, identifying spatially and transcriptionally distinct sub-populations within the anterior scl-expressing cells in vivo. I have identified regulatory programmes underlying development of anterior vascular and haematopoietic progenitors, and identified a cell subpopulation co-expressing key regulators of both lineages, possibly accounting for the developmental plasticity within the system. Here, scl-expressing haematopoietic progenitor populations were profiled at unparalleled temporal and spatial resolution, obtaining full genome-wide description of early vertebrate primitive haematopoiesis in vivo. This work provides comprehensive framework for analysis of gene regulatory interactions and exploration of novel factors and putative regulatory elements involved in this process.

Authors: Wheatley, L

• Type of award: DPhil
• Level of award: Doctoral
• Awarding institution: University of Oxford
• Language: English
• Keywords: Developmental biology; Haematopoiesis; Zebrafish
• Subjects: Developmental genetics