Stem cell self-renewal in haematopoiesis
Haematopoietic stem cells (HSC) provide a lifelong supply of blood and immune cells. While they continuously produce specialised cells, they also replenish a pool of stem cells in the bone marrow, a property known as self-renewal. Thanks to this property, bone marrow or cord blood transplantation provide a life-saving treatment for blood and immune-related diseases. Unfortunately, donor-matching or insufficient number of cells still render these therapies unfeasible or unsuccessful for certain patients.
Attempts to overcome these limitations have been unable to create or expand in a dish a reliable source of blood stem cells for patients, mostly because of defective self-renewal. Our research focuses on understanding the establishment and maintenance mechanisms that endow human HSC self-renewal, as determined by the expression of specific genes sets that define HSC function. We investigate the regulation of the expression of such HSC-defining genes, how the environment and the metabolism affect this regulation, and how attempts to make or maintain these cells in vitro can be improved to preserve their stemness. By gaining a better understanding of HSC biology, our studies aim to contribute to the development of novel HSC-based therapies.
Calvanese V, et al (2022). Mapping human haematopoietic stem cells from haemogenic endothelium to birth. Nature, 604, 534–540. PMID: 35418685 DOI: 10.1038/s41586-022-04571-x
Calvanese V, et al (2019). MLLT3 governs human haematopoietic stem-cell self-renewal and engraftment. Nature, Dec;576(7786):281-286. doi:10.1038/s41586-019-1790-2. PMID: 31776511
Ng ES, et al (2016). Differentiation of human embryonic stem cells to HOXA+ hemogenic vasculature that resembles the aorta-gonad-mesonephros. Nature Biotech, Nov;34(11):1168-1179. PMID: 27748754.
Dou DR, et al (2016). Medial HOXA genes demarcate haematopoietic stem cell fate during human development. Nat Cell Biol , Jun;18(6):595-606. PMCID:PMC4981340.
Calvanese V, et al. (2012). A promoter DNA demethylation landscape of human hematopoietic differentiation. Nucleic Acids Research, Jan 1;40(1):116-131. PMC3245917
Somatic stem cells
Stemness and differentiation
High throughput screening
Uchenna Okpechi (Research assistant)
Aisling Fairweather (Research assistant)
Andrew Elefanty, MCRI, Australia
Hanna Mikkola, UCLA Broad Stem Cell Center, USA
Katja Schenke-Leyland, University Women's Hospital Tubingen, Germany