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Blood and cardiovascular development, with a particular focus on stem cells. Transcriptional network assembly in response to embryonic signals. Xenopus and zebrafish models.

Patchwork heart

The lab has two points of focus – the ontogeny of haematopoietic stem cells and heart regeneration.

Haematopoiesis

We are studying the embryonic signals and nuclear responses involved in the programming of blood stem cells during development.  An understanding of the mechanism by which these cells are prevented from differentiating will serve as a paradigm for stem cells in general and facilitate manipulation of these important cells for regenerative medicine.  Their genesis in the embryo begins with the formation of cells with blood and endothelial potential in the lateral plate mesoderm which differentiate as arterial endothelium before an epithelial to haematopoietic transition takes place in the floor of the dorsal aorta. We and others have identified many of the signals driving this process and the responding transcription factors that establish the regulatory networks in the nucleus, and we are beginning to model the process. In addition to stem cell ontogeny, we have begun to investigate the decisions taken by the stem cells as they migrate to their final resting place. In particular, we are interested in where and how they expand, a property of immense value in the clinic.

Heart regeneration

When cardiac muscle is damaged, upon coronary artery blockade for example, the lost cells are never replaced. In contrast, when cells are killed or removed from the zebrafish heart, the lost muscle is regenerated and normal function is resumed. Understanding the basis of this regeneration could suggest approaches to achieving repair of human hearts. We are studying various aspects of this process ranging from the cells recruited in to regenerate, the signals controlling that recruitment and the genetic programme induced. We are making liberal use of transgenic lines of zebrafish expressing fluorescent reporters, which allow us to follow the cells during recovery in the optically transparent embryos and adults. We are also perturbing candidate signals and their nuclear targets, the transcription factors. Through collaborations we are comparing the situation in zebrafish with those in mice, as well as humans, where regeneration is possible for the first seven days after birth but then lost.

Our team

Selected publications

Collaborations

Prof Marella de Bruijn (WIMM)

Prof Catherine Porcher (WIMM)

Prof Tatjana Sauka-Spengler (WIMM)

Prof Paul Riley (Department of Pathology Anatomy and Genetics, DPAG)

Related research themes