Speaker: Xiaoyi (Chelsea) Cheng, graduate candidate in Espin Palazon Lab

Title: "Nod1 and Nod2: A synergistic regulation of HSPC specification"

Abstract: Hematopoiesis is the process by which all blood cells are produced and developed from hematopoietic stem and progenitor cells (HSPCs) in the bone marrow. This process is crucial for maintaining body’s immune response, tissue repair and oxygen transport and homeostasis by continuously replenishing the supply of all blood cells. HSPC specification is thus a critical process, in which multipotent stem cells in the hemogenic endothelium (HE) transition into functional HSPCs. The specification of HSPCs is tightly regulated by various molecular mechanisms and different signaling pathways. Thus, understanding the regulation processes of HSPC specification if essential in advancing clinical therapies against blood disorders.

In this thesis, we highlight the distinct roles for Nucleotide-binding oligomerization domain-containing protein (Nod) 1 and Nod2 pathways in regulating HSPC specification. Using zebrafish as a model organism, our studies revealed that early activation of the Rac1-Nod1-Ripk2-NF-kB axis in endothelial cells (ECs) primes them towards a definitive HE fate, which is a prerequisite for HSPC specification. In addition, we identified that Nod2 acts through the Ripk2-Erk signaling pathway to regulate HSPC formation during early EHT by favoring erythroid-biased over myeloid-biased HSPC specification.

Together, these findings underscore the roles of Nod1 and Nod2 in HSPC specification and HSPC heterogeneity establishment. These advancements enhance our current understanding of HSPC formation mechanisms and contribute to the protocols in generating patient-specific and functional HSPCs from human induced pluripotent stem cell (iPSCs) for blood disorder treatments.

Webex link: https://iastate.webex.com/meet/xcheng