Open or closed: Investigating the transcriptome and epigenome of embryonic hematopoiesis at single cell resolution

MOK_U23DTP2

Hematopoiesis is a dynamic process by which all blood cells are generated during the lifetime of an organism.

Blood cells are closely regulated by changes in the transcriptome and epigenome.

Understanding how blood cells form is of fundamental importance and clinically relevant for the progress of cell replacement therapies and transplantation protocols in blood and vascular genetic- and age-related diseases.

While the major anatomical sites of hematopoiesis change during a lifetime, the developmental origin of these cells remain not fully determined. Furthermore, the gene regulatory networks involved in early specification of these cells is also unresolved.

Using the avian (chicken) embryo as a model organism, we propose to comprehensively define the hematopoietic genetic programming, concentrating on the early stages of embryonic development.

Together with colleagues at the Earlham Institute we will use state-of-the-art single-cell RNA-sequencing to determine the key genes and use single-cell ATAC-sequencing to identify non-coding regulatory elements followed by detailed bioinformatic analyses.

We will validate key gene networks with in vivo experimentation using genome-editing tools (such as CRISPR) and advanced live microscopy.

Many of the molecular processes involved in cellular reprogramming are conserved during evolution and is likely that at least some of the discoveries made in the avian model will have direct relevance to humans.

We are looking for a motivated, imaginative, and ambitious student to create and analyse single-cell sequencing datasets and validate findings for in vivo functional analysis.

This is a joint project between groups of Gi Fay Mok at the BioMedical Research Centre (UEA), Iain Macaulay and Wilfried Haerty (both EI) and Andrea Münsterberg (UEA).

The student will acquire bench and bioinformatic training as well as excellent personal and professional development training offered by UEA, EI and the NRPDTP.
Contact Dr Gi Fay Mok (g.mok@uea.ac.uk) for more information and discussions about the project.

References

Louise Smith, E., Mok, G. F., & Münsterberg, A. (2022). Investigating chromatin accessibility during development and differentiation by ATAC-sequencing to guide the identification of cis-regulatory elements. Biochemical Society transactions, 50(3), 1167–1177. https://doi.org/10.1042/BST20210834.

Mok, G. F., Folkes, L., Weldon, S. A., Maniou, E., Martinez-Heredia, V., Godden, A. M., Williams, R. M., SaukaSpengler, T., Wheeler, G. N., Moxon, S., & Münsterberg, A. E. (2021). Characterising open chromatin in chick embryos identifies cis-regulatory elements important for paraxial mesoderm formation and axis extension. Nature communications, 12(1), 1157. https://doi.org/10.1038/s41467-021-21426-7.

Mok, G. F., McColl, J., & Münsterberg, A. (2021). 4D Live Imaging and Analysis of Chick Embryo Somites. Methods in molecular biology (Clifton, N.J.), 2179, 173–181. https://doi.org/10.1007/978-1-0716-0779-4_15.

Mok, G. F., Lozano-Velasco, E., Maniou, E., Viaut, C., Moxon, S., Wheeler, G., & Münsterberg, A. (2018). miR-133- mediated regulation of the Hedgehog pathway orchestrates embryo myogenesis. Development (Cambridge, England), 145(12), dev159657. https://doi.org/10.1242/dev.159657.

Goljanek-Whysall, K., Mok, G. F., Fahad Alrefaei, A., Kennerley, N., Wheeler, G. N., & Münsterberg, A. (2014). myomiR-dependent switching of BAF60 variant incorporation into Brg1 chromatin remodeling complexes during embryo myogenesis. Development (Cambridge, England), 141(17), 3378–3387. https://doi.org/10.1242/dev.108787.