Dausinas, PaigeHartman, MelissaAllman, LaurenO'Leary, Heather2023-06-262023-06-262021Dausinas P, Hartman M, Allman L, O'Leary H. 3058 – SARS-COV-2 BINDING IN HEMATOPOIETIC STEM AND PROGENITOR CELLS UNDER LOW OXYGEN CONDITIONS. Exp Hematol. 2021;100:S70. doi:10.1016/j.exphem.2021.12.276https://hdl.handle.net/1805/33958This article is made available for unrestricted research re-use and secondary analysis in any form or be any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.The SARS-CoV-2 pandemic highlighted a need for in-depth understanding of interaction/identification of receptors and mechanisms/functional consequences of viral binding/entry. SARS-CoV-2 spike protein (SBP) facilitates viral entry via ACE2 and/or NRP1 binding, with DPP4 as a potential co-receptor. These binding partners are expressed on various cell types including hematopoietic stem and progenitor (HSC/HSPC) cells [1-3]. HSC/HSPCs generate blood cells and reside in the low oxygen (lowO2, 1-4%) bone marrow niches that provide critical signals for maintenance, self-renewal, and differentiation. To investigate aspects of SARS-CoV-2 interactions with HSC/HSPC such as endogenous receptor expression, SPB binding and subsequent functional alterations in native low O2, we performed transcriptional and phenotypic/functional analysis. In lowO2, we identified increased surface expression of ACE2, DPP4 and NRP1, and enhanced binding of SBP to HSC/HSPC populations which amplified proliferation of SBP bound in lowO2. ACE2 and DPP4 surface expression were ∼2-fold higher in HSPCs (p=0.017, p=0.001) and HSCs (p=0.010, p=0.03), and NRP1 was ∼1.5-fold (p=0.002) higher in HSPCs in lowO2 compared to air. Interestingly, in lowO2, overall SBP binding was enhanced in HSPC (2.2-fold, p<.001) and HSC (2.6-fold, p=.018). Although not all cells expressing ACE2/DPP4/NRP1 bind SBP (∼50%), all cells exhibiting SBP binding in HSC/HSPC populations are triple positive for ACE2, NRP1, and DPP4. Additionally, we observed greater than a 2-fold increase in proliferation of SBP bound vs unbound cells in replating assays in lowO2 (p<.001). These data impart compelling evidence that SBP binding/functional outcomes are unique in low O2, providing a foundation that may have potential clinical implications for COVID19 treatment and expanding our baseline understanding of SARS-CoV-2 viral binding implications.en-USPublic Health EmergencyViral bindingViral entrySpike proteinsBinding partnersSARS-CoV-2Other