Group Leader

Dr. Eirini Trompouki
Dr. Eirini Trompouki
Group Leader
Phone:+49 761 5108-550

Lab Eirini Trompouki

Laboratory Eirini Trompouki

Header image 1470662514

Regulation of embryonic and adult hematopoiesis

Hematopoietic Stem Cells (HSCs) provide the foundation of the hematopoietic system in vertebrates. Being multipotent and capable of self-renewal, HSCs are responsible for constant production of all blood cell types throughout life. Because of their properties, HSCs are highly demanded in clinic daily.

For example, HSCs are used for replenishing the hematopoietic system of acute myeloid leukemia (AML) patients after chemotherapy or for patients that need blood transfusions. However, due to their limited number and our inability to expand them sufficiently in vitro it is impossible, right now, to provide for these extensive needs. In addition, alterations in the properties of HSCs and their environment lead to disease.

In order to be able to expand HSCs or cure hematopoietic malignancies arising from them, we need to understand the network of signals that govern their fate from the time they develop till maturity. HSCs are initially generated during embryonic development, as proliferative cells that create the HSC pool of a vertebrate organism. During adulthood they reside in the bone marrow as quiescent HSCs and exit this state, almost exclusively, in case of stress or disease.

In mice and zebrafish, HSCs are generated in the aorta-gonad-mesonephros (AGM) region from endothelial cells in a process termed endothelial-to-hematopoietic transition (EHT). Multiple conserved signaling pathways governing EHT were identified in the recent years. For instance, Wnt, BMP, Vegf, and Notch signaling pathways are absolutely required for HSC emergence and have been utilized in attempts to generate functional HSCs from pluripotent stem cells in vitro.

Figure 1: Different model organisms help to answer complex questions. In this figure zebrafish and mouse embryos are used to study hematopoiesis. Zoom Image
Figure 1: Different model organisms help to answer complex questions. In this figure zebrafish and mouse embryos are used to study hematopoiesis.

Due to the high complexity of HSC ontogeny, these approaches have thus far proven unsuccessful, indicating that missing key signals are yet to be discovered. Therefore, our first goal is to delineate precisely the mechanisms involved in HSC emergence in vivo and improve current strategies. In addition, many of these signaling networks that affect HSC ontogeny, play a role in HSC maintenance during adulthood. Our studies extend also to adult hematopoiesis, in an effort to create a temporal (from embryo till adult) signaling network imperative for hematopoiesis. Finally, we combine our results with published databases to study specific transcription factor networks that are deregulated in hematopoietic diseases. Our main goal is to identify combinations of mutated or deregulated transcription factors and unravel how they can lead to disease.

 
loading content
Go to Editor View