Regulation of definitive hematopoiesis by Apelin and Tbx20 signaling

• Applicant: Professor Dr. Christian Helker
• Subject Area: Developmental Biology
• Term: since 2025
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 565709759

Definitive hematopoiesis, in which hematopoietic stem and progenitor cells (HSPCs) develop, is essential for vertebrate development and lifelong blood cell production. During embryogenesis, HSPCs originate from a specialized subset of endothelial cells, termed hemogenic endothelial cells (HECs), through endothelial-to-hematopoietic transition (EHT). While the key transcriptional regulators of EHT, such as Runx1 and Gata2, are well established, the mechanisms that define endothelial cell fate and restrict hematopoietic commitment remain poorly understood. This knowledge gap presents a major obstacle in efforts to understand these cell fate decisions at the cellular and molecular level. To bridge this gap, we investigate the molecular factors that orchestrate EHT and cell fate decisions in the embryonic dorsal aorta (DA). We hypothesize that a Apelin-Tbx20 axis acts as a molecular switch balancing endothelial and hematopoietic differentiation. Using the zebrafish model, which offers genetic conservation with mammals, live imaging capabilities, and well-established transgenic lines, we will dissect the spatio-temporal dynamics of Tbx20 during EHT. Our study will investigate how endothelial cells are instructed to either maintain their vascular identity or transition into hematopoietic stem cells. These findings will provide fundamental insights into blood stem cell development and the molecular pathways that orchestrate cell fate decisions during embryogenesis.

• DFG Programme: Research Grants