Human Hematopoietic Stem, Progenitor, and Immune Cells Respond Ex Vivo to SARS-CoV-2 Spike Protein
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Human Hematopoietic Stem, Progenitor, and Immune Cells Respond Ex Vivo to SARS-CoV-2 Spike Protein James Ropa 1 & Scott Cooper 1 & Maegan L. Capitano 1 & Wouter Van’t Hof 2 & Hal E. Broxmeyer 1 Accepted: 5 October 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Despite evidence that SARS-CoV-2 infection is systemic in nature, there is little known about the effects that SARS-CoV-2 infection or exposure has on many host cell types, including primitive and mature hematopoietic cells. The hematopoietic system is responsible for giving rise to the very immune cells that defend against viral infection and is a source of hematopoietic stem cells (HSCs) and progenitor cells (HPCs) which are used for hematopoietic cell transplantation (HCT) to treat hematologic disorders, thus there is a strong need to understand how exposure to the virus may affect hematopoietic cell functions. We examined the expression of ACE2, to which SARS-CoV-2 Spike (S) protein binds to facilitate viral entry, in cord blood derived HSCs/HPCs and in peripheral blood derived immune cell subtypes. ACE2 is expressed in low numbers of immune cells, higher numbers of HPCs, and up to 65% of rigorously defined HSCs. We also examined effects of exposing HSCs/HPCs and immune cells to SARS-CoV-2 S protein ex vivo. HSCs and HPCs expand less effectively and have less functional colony forming capacity when grown with S protein, while peripheral blood monocytes upregulate CD14 expression and show distinct changes in size and granularity. That these effects are induced by recombinant S protein alone and not the infectious viral particle suggests that simple exposure to SARS-CoV-2 may impact HSCs/HPCs and immune cells via S protein interactions with the cells, regardless of whether they can be infected. These data have implications for immune response to SARS-CoV-2 and for HCT. Keywords SARS-CoV-2 . COVID-19 . Spike protein . ACE2 . Hematopoietic stem and progenitor cells . Hematopoiesis . Immune cells . Cord blood . Hematopoietic cell expansion
Introduction The devastating effects of coronavirus disease 2019 (COVID19) caused by severe acute respiratory coronavirus 2 (SARSCoV-2) infection highlights the need to understand the virus’s This article belongs to the Topical Collection: Special Issue on COVID19 Pandemic and Stem Cells Guest Editor: Mariusz Z. Ratajczak Electronic supplementary material The online version of this article (https://doi.org/10.1007/s12015-020-10056-z) contains supplementary material, which is available to authorized users. * James Ropa [email protected] * Hal E. Broxmeyer [email protected] 1
Department of Microbiology and Immunology, Indiana University School of Medicine, 950 West Walnut Street, R2-302, Indianapolis, IN 46202-5181, USA
2
Cleveland Cord Blood Center, Cleveland, OH, USA
effect on host tissues [1–3]. One of the alarming aspects of COVID-19 is the systemic nature of the disease and the paucity of information available regarding effects of infection on many different host cell types [4, 5]. He
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