The niche effect: study of the cellular and extracellular microenvironment of foetal liver that promotes haematopoietic stem cell expansion.

Haematopoietic stem cells (HSCs) form during embryogenesis and produce blood cells throughout foetal and adult life through a complex and hierarchical process named haematopoiesis. The foetal liver (FL) is the primary foetal haematopoietic organ responsible for HSC expansion and differentiation, FL-HSCs then migrate to the bone marrow (BM), the site of adult haematopoiesis. The BM microenvironment, composed of extracellular matrix (ECM) and stroma cells, directs HSC homeostasis. Despite extensive understanding of the BM-niche, little is known about the factors supporting HSC expansion in the foetal liver. Studies suggest a dynamic interplay between FL-cells controlling hepatogenesis and haematopoiesis, however the role of specific microenvironmental cues supporting these processes remains unknown. The aim of this project is to understand the complex microenvironment supporting HSC self-renewal during development in the foetal liver. The role of ECM-proteins and how they impact haematopoiesis via matrix molecular and mechanical signalling will be investigated using established tissue engineered models. The FL-niche will be deconstructed and re-built step-by-step to understand the minimal cellular and protein components essential for HSC homeostasis and self-renewal. The study will provide novel data regarding HSCs expansion which will be used to advance HSC-based therapies.