Research Topics

Hemato-vascular development in vertebrates

©UNIGE – Bertrand Lab. The thymus of a zebrafish at 4.5 days post fertilization showing immature lymphoid progenitors (Ikaros:GFP, green) differentiating into T cell progenitors (Rag2:DsRed, pink).

Prof. Bertrand's laboratory is mostly interested in understanding the molecular pathways involved in hematopoietic stem cells (HSC) specification, development, expansion, migration and differentiation, by using the zebrafish as a model of experimentation and by translating to in vitro models using human cells, in agreement with the 3Rs (Reduce, Replace, Refine). The inflammatory pathways are of particular interest, as they regulate numerous aspects of the interactions between HSCs and their different microenvironments.

The research team has shown that the caudal hematopoietic tissue (CHT) vasculature expresses a specific transcription factor, tfec, that controls the expression of a variety of genes known to be involved in the immune response. They are currently trying to understand their roles in HSC expansion in the CHT. Indeed, they found that ifi30/gilt is important to dampen reactive oxygen species levels in the hematopoietic niche and therefore protect HSCs. They are now studying the effect of many other proteins from the immune toolbox in this particular process, with the goal of translating their findings to human HSC expansion.

In parallel, they are working on the characterization of innate lymphoid cells in the zebrafish, to understand their development and their function throughout evolution. They have identified many new genes of interest (through single cell RNA sequencing) and are currently building new transgenic animals to mark and follow these cells in vivo.

Specific expertise

Hematopoiesis, hematopoietic stem cells, mouse embryogenesis, zebrafish, sterile inflammation, hematopoietic stroma, hematopoietic cell culture, transgenesis, CRISPR/Cas9.

Selected Publications

A connexin/ifi30 pathway bridges HSCs with their niche to dampen oxidative stress. 
Cacialli P, Mahony CB, Petzold T, Bordignon P, Rougemont AL, Bertrand JY. Nat Commun. 2021 Jul 23;12(1):4484. doi: 10.1038/s41467-021-24831-0. PMID: 34301940
The macrophage-expressed gene (mpeg) 1 identifies a subpopulation of B cells in the adult zebrafish. 
Ferrero G, Gomez E, Lyer S, Rovira M, Miserocchi M, Langenau DM, Bertrand JY, Wittamer V. J Leukoc Biol. 2020 Mar;107(3):431-443. doi: 10.1002/JLB.1A1119-223R. Epub 2020 Jan 7.
Embryonic Microglia Derive from Primitive Macrophages and Are Replaced by cmyb-Dependent Definitive Microglia in Zebrafish. 
Ferrero G, Mahony CB, Dupuis E, Yvernogeau L, Di Ruggiero E, Miserocchi M, Caron M, Robin C, Traver D, Bertrand JY, Wittamer V. Cell Rep. 2018 Jul 3;24(1):130-141. doi: 10.1016/j.celrep.2018.05.066.
tfec controls the hematopoietic stem cell vascular niche during zebrafish embryogenesis. 
Mahony CB, Fish RJ, Pasche C, Bertrand JY. Blood. 2016 Sep 8;128(10):1336-45. doi: 10.1182/blood-2016-04-710137. Epub 2016 Jul 11.
March 24, 2022
  Immune cell trafficking and maturation