Speaker: Abbigail McCune, Ph.D. graduate candidate in Espin Palazon Lab

Title: "A tale of two inflammatory genes: Investigating the role of grna and stat3 in myelopoiesis"

Abstract: Embryonic myelopoiesis is a carefully regulated process that provides early hematopoietic populations critical for an organism's proper development and survival.  Myelopoiesis is defined by three distinct waves: primitive, transient, and definitive. Temporal dynamics, anatomical origin, progenitor populations, and the longevity of the produced cells define these waves. As the hematopoietic progenitors from these waves differentiate into terminal identities, they face several developmental bifurcation points where the decision between lineage and final cell identity is regulated by the expression of various signals, including various transcription factors and inflammatory signals. We clarify the role of one specific inflammatory signal, Grna, which was previously identified as necessary for myeloid differentiation at the expense of the erythroid program. Previously, only its general role in embryonic myeloid differentiation was established. We demonstrate using the zebrafish model, Grna depletion, lineage tracing, and flow cytometry, that these effects on early myeloid populations are mediated through the transient wave, with erythromyeloid progenitors (EMPs) being driven towards terminal myeloid identity. We establish a proposed model whereby grna influences the beginning of the definitive wave by driving differentiation of the EMP-derived macrophage population. Through the production of grna, these macrophages regulate NF-kB activity in the hemogenic endothelium of the ventral dorsal aorta, enabling proper determination of hematopoietic stem and progenitor cells (HSPCs). To address the molecular mechanism behind grna-mediated myelopoiesis, we propose a model where Jak2a-Stat3 signaling mediates grna expression, which then enhances the transcriptional activity of Stat3 to drive EMP-derived myeloid differentiation. We utilize this mechanism to explain further the role of Grna and Stat3 in wound healing as we demonstrate that EMP-derived macrophages are the main contributor to embryonic wound healing.