Dr Simón Méndez-Ferrer
Blood stem cell niches
Laboratory: Cambridge Blood Centre, NHS Blood and Transplant, Cambridge Biomedical Campus. Departmental Affiliation: Haematology
Méndez-Ferrer has discovered a connection with bone marrow, the brain and other systemic signals which controls the behaviour of blood stem cells. His research has contributed to the dissection of the "niches" in which stem cells reside and to the understanding of the role of these niches in the development of myeloproliferative diseases.
ERC, Howard Hughes Medical Institute
Peri-vascular nestin+ niche stem cells are innervated by sympathetic fibers in the bone marrow. Projection stack (~100μm) of fluorescent images showing the distribution of Nestin-GFP+ cells (green), CD31/PECAM+ vascular endothelial cells (blue) and tyrosine hydroxylase+ sympathetic nerve fibers (red) after whole mount staining of the skull bone marrow. (Credit Isern and Méndez-Ferrer, Curr Osteoporos Rep. 2011 Dec;9(4):210-8.)
The Méndez-Ferrer laboratory research focuses on the regulation of the haematopoietic stem-cell niche in health and disease. Blood stem cells reside in specialised niches which allows them to self-renew, proliferate, differentiate and migrate according to the organism's requirements. The group studies multisystem regulatory mechanisms by which the haematopoietic stem cell niche fulfils these complex functions and how the deregulation of these mechanisms contributes to haematological disorders. The group has demonstrated that the brain regulates a peripheral stem cell niche in the bone marrow partly through sympathetic innervation of nestin+ niche cells. Protection of this regulatory network, whose constituents might share a related ancestry, can block the manifestation of myeloproliferative neoplasms. Our research indicates that neuroendocrine regulation of bone marrow stem cells by adrenergic signals or by sex hormones could potentially offer novel therapeutic approaches. We study the interaction of mesenchymal and haematopoietic stem cells and its implications for bone marrow transplantation procedures and the development of myeloproliferative neoplasias.
Claire Fielding, Dorian Forte, Anne Francis, María García-Fernández, Andrés García-García, Claudia Körn, Tom McKerrell, Justyna Rak
Our research focuses on the regulation of the environment (‘niche’) in which the blood stem cells reside both in health and disease. Blood stem cells are located in specialised niches which allow them to function according to the organism's requirements. We study the mechanisms of how the stem cell niche fulfills these complex functions. Through this, we aim to understand how the disruption of these mechanisms contributes to blood disorders.
- Del Toro R, Chèvre R, Rodríguez C, Ordóñez A, Martínez-González J, Andrés V, Méndez-Ferrer S. Nestin(+) cells direct inflammatory cell migration in atherosclerosis. Nat Commun. 2016 Sep 2;7:12706. doi: 10.1038/ncomms12706. PMCID:PMC27586429
- Sánchez-Aguilera A, Arranz L, Martín-Pérez D, García-García A, Stavropoulou V, Kubovcakova L, Isern J, Martín-Salamanca S, Langa X, Skoda RC, Schwaller J, Méndez-Ferrer S. Estrogen signaling selectively induces apoptosis of hematopoietic progenitors and myeloid neoplasms without harming steady-state hematopoiesis. Cell Stem Cell 15: 791-780, 2014. PMID:25479752
- Isern J, García-García A, Martín AM, Arranz L, Martín-Pérez D, Torroja C, Sánchez-Cabo F, Méndez-Ferrer S. The neural crest is a source of mesenchymal stem cells with specialized haematopoietic stem cell niche function.eLife Sept 25, 2014 PMCID:PMC4381911
- Arranz L, Sánchez-Aguilera A, Martín-Pérez D, Isern J, Langa X, Tzankov A, Lundberg P, Muntión S, Tzeng Y-S, Lai D-M, Schwaller J, Skoda RC, Méndez-Ferrer S. Neuropathy of haematopoietic stem cell niche is essential for myeloproliferative neoplasms. Nature 512: 78-81, 2014. PMID:25043017
- Méndez-Ferrer S, Michurina TV, Ferraro F, Mazloom AR, MacArthur BD, Lira SA, Scadden DT, Ma’ayan A, Enikolopov GN, Frenette PS (2010). Mesenchymal and haematopoietic stem cells form a unique bone marrow niche. Nature 466:829-834 PMCID:PMC3146551