FLI Colloquium with Elisa Gomez Perdiguero

The hematopoietic system develops from sequential and overlapping waves of progenitors. Transient hematopoietic progenitor waves, such as primitive cells and definitive erythromyeloid progenitors (EMPs) form the extraembryonic yolk sac, sustain the fetus throughout pregnancy until birth. Afterward, intraembryonic-derived hematopoietic stem and progenitor cells (HSPCs) take over blood cell production. How transient progenitors and HSPCs cooperate/compete in the fetal liver to build the immune system is still poorly understood. Importanlty, even though yolk sac hematopoiesis is transient, EMP-derived cells remain in postnatal and adult tissues, in particular EMP-derived macrophages and to a lesser extent mast cells. Therefore, perturbations in EMPs could therefore affect the organism not only during the developmental period but also long-term postnatally. 

First, Elisas Lab hypothesized that functional EMP hematopoiesis is required not only to produce fetal blood cells but also to ensure the expansion and commitment of fetal HSC. They thus perturbated EMP-derived hematopoiesis and probed whether HSC commitment was altered during fetal and adult life. Depletion of EMP-derived macrophages with a Csf1r inhibitor led to precious differentiation of fetal HSCs and to a long-term reduction in lymphoid-biased multipotent progenitors (MPP4) as well as an increased efficiency in myeloid differentiation in vitro from adult bone marrow progenitors. For the macrophage aficionados, EMP-derived macrophages that survived the Csf1r depletion outcompeted HSC-derived macrophages in postnatal life.

Second, through lineage tracing and single cell RNA/ATAC-sequencing,  Elisas team discovered that EMP-derived and HSPC-derived fetal megakaryocytes (Mk) followed distinct developmental trajectories. They then tested the functional relevance of these trajectories by inducing a Gata1 mutation. Ontogeny, or the Mk biography, dictated the response to mutant Gata1, with a strong accumulation of primitive- and EMP- but not HSPC-derived megakaryocytes. Mutant Gata1 also caused the development of blast-like cells exclusively in yolk sac-derived lineages.

The FLI Colloquium will be a hybrid event. Details for accessing the session will be provided before the colloquium takes place. For external guests: Please contact Ivonne Roeppnack-Jahnke for details.