Alexander Medvinsky Research Group
Ontogeny of haematopoietic stem cells
Haematopoietic stem cells (HSCs) developing in the embryo ultimately give rise to the adult haematopoietic system. The main direction of our research is to investigate cellular and molecular mechanisms involved in the generation and expansion of definitive HSCs in the mammalian embryo.
Aims and areas of interest
Our specific aims are to
- Phenotypically characterize and visualize primary definitive HSCs in the early embryo
- Identify embryonic ancestor cells which develop into HSCs
- Identify routes and mechanisms of hematopoietic stem cell migration
- Identify and characterize transcription and growth factors as well as extracellular signaling and matrix molecules responsible for the process of initiation, expansion and migration of HSCs.
- Based on the knowledge of mechanisms underlying development of HSCs in vivo, develop new protocols for generation of definitive long-term repopulating HSCs from ES cells (so far attempts to achieve this by different laboratories without employing genetic intervention have been unsuccessful).
Haematopoietic stem cells (HSCs) developing in the embryo ultimately give rise to the adult haematopoietic system. The main direction of our research is to investigate cellular and molecular mechanisms involved in the generation and expansion of definitive hematopoietic stem cells (HSC) in the mammalian embryo.
Approach and progress
We broadly use methods of embryo manipulations, molecular biology, experimental haematology and bioinformatic analysis to understand early HSC development. We have identified the AGM region as a specific niche for HSC development in the mouse and in the human (Medvinsky et al., Nature 1993; Medvinsky and Dzierzak, Cell, 1996; Ivanovs et al., J. Exp. Med. 2011; Ivanovs et al., Stem Cell Reports, 2014). We develop novel methods which allow us to recapitulate and analyse the process of early HSC development in vitro (Taoudi et al., Cell Stem Cell, 2008; Rybtsov et al., J Exp Med., 2011; Rybtsov et al., Stem Cell Reports, 2014). We investigate inductive interactions and asymmetric signalling within the AGM region that underlie development of HSCs in during mouse and human embryogenesis (McGarvey et al., J Exp Med., 2017; Souilhol et al., Nat. Comm., 2016; Crosse et al., Cell Stem Cell, 2020). Building up on our expertise, we are currently investigating molecular and cellular mechanisms of human ES cell differentiation into blood with the ultimate goal to generate HSCs in the Petri dish for transplantation in clinics.
Nneka Concilia Nnadi (PhD Student)
Sabrina Gordon-Keylock (Postdoc)
Adelle Greene (PhD Student)
Stanislav Rybtsov (Postdoc)
Alexandre Meier (PhD Student)