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- Nerlov Group: Hematopoietic Stem Cell Genetics Research Group
Professor of Stem Cell Biology
The hematopoietic stem cell is capable of maintaining the output of >10 cellular lineage for the entire lifespan of the organism. This is made possible by the presence of structures (niches) dedicated to long-term maintenance of the multi-potent stem cell state, as well as mechanisms for the generation and subsequent lineage specification of stem cell progeny lacking long-term self-renewal capacity.
We use genetic methods, combined with genome-wide gene expression and chromatin profiling, to address the complexity of the hematopoietic stem cell population, the niches that maintain them, and the changes hematopoietic stem cells and niches undergo during aging. We investigate the regulators (transcription factors, signaling molecules) that control the lineage commitment of multi-potent hematopoietic progenitors, as well as the cellular pathways that they specify. Finally, we model how mutations affecting the normal transcriptional control of myelopoiesis result in acute myeloid leukemia, and address how the leukemic stem cells responsible for the disease are maintained.
The final goal is to understand the molecular basis for and spatial organization of normal, aging and malignant hematopoiesis, and to use this knowledge to devise cell based and molecular therapies that can be used to treat hematopoietic insufficiencies and malignancies.
Distinct myeloid progenitor-differentiation pathways identified through single-cell RNA sequencing.
Drissen R. et al, (2016), Nat Immunol, 17, 666 - 676
A dynamic niche provides Kit ligand in a stage-specific manner to the earliest thymocyte progenitors.
Buono M. et al, (2016), Nat Cell Biol, 18, 157 - 167
Wnt/β-Catenin Signaling Induces Integrin α4β1 in T Cells and Promotes a Progressive Neuroinflammatory Disease in Mice.
Sorcini D. et al, (2017), J Immunol
Niche-mediated depletion of the normal hematopoietic stem cell reservoir by Flt3-ITD-induced myeloproliferation.
Mead AJ. et al, (2017), J Exp Med, 214, 2005 - 2021
A transit-amplifying population underpins the efficient regenerative capacity of the testis.
Carrieri C. et al, (2017), J Exp Med, 214, 1631 - 1641
Insights into specificity, redundancy and new cellular functions of C/EBPa and C/EBPb transcription factors through interactome network analysis.
Cirilli M. et al, (2017), Biochim Biophys Acta, 1861, 467 - 476
Initial seeding of the embryonic thymus by immune-restricted lympho-myeloid progenitors.
Luis TC. et al, (2016), Nat Immunol, 17, 1424 - 1435