Poster abstracts
Poster number 97 submitted by Rakeb Tafesse
Understanding the role of EGFL7 in HSC precursors during HSC specification in the AGM
Rakeb Tafesse (The Ohio State University), Chinmayee Goda (The Ohio State University), Rohan Kulkarni (The Ohio State University), Girish Rajgolikar (The Ohio State University), Malith Karunasiri (The Ohio State University), Adrienne Dorrance (The Ohio State University)
Abstract:
In the hematological transplantation field, novel methods are needed to expand and maintain functional hematopoietic stem cells (HSCs) to increase the number of transplantable HSCs and potentially improve outcomes for patients1,2. Further understanding of factors and pathways that are capable of regulating HSC formation and/or functions is a critical step towards achieving the end goal of having successful hematopoietic stem cell transplantation (HSCT). Our unpublished data show that the lack of epidermal growth factor like 7 (EGFL7), a predominantly endothelial cell secreted protein, in adult mice led to a significant decrease in HSC numbers. In addition, in vivo treatment of wild type (WT) mice with exogenous EGFL7 or recombinant EGFL7 (rEGFL7) resulted in a significant increase in HSC numbers and enhanced their functions, such as having a higher engraftment capacity when transplanted into recipient mice compared to mice transplanted with PBS treated bone marrow cells. Furthermore, treating cells from the aorta-gonad-mesonephros (AGM)-site of HSC formation- of the E11.5 mouse embryo with rEGFL7 in vitro resulted in a higher percent of HSCs and primitive hematopoietic cells. EGFL7 is essential for embryogenic vascular formation, and its mRNA is expressed within the AGM3-5. Our group and others have also shown that EGFL7 is capable of binding to signaling receptors like Notch, which are important in normal hematopoiesis6,7. Specifically, Notch1 within the AGM has been shown to be critical during HSC formation from HSC precursors (HPs) (pro-HSC, pre-HSC type I and II) in the mouse embryo8,9. Here we hypothesize that the significant reduction of HSCs that we have observed in the adult Egfl7 -/- mice originate at the HPs, and the mechanism is at least in part being regulated by Notch1. We will test this hypothesis by isolating HPs from WT and Egfl7 -/- mice AGMs to assess their numbers and functions, as well as interrogating EGFL7-Notch1 interaction and downstream gene expression changes in the AGM.
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