Human Hematopoietic Stem, Progenitor, and Immune Cells Respond Ex Vivo to SARS-CoV-2 Spike Protein.
Human Hematopoietic Stem, Progenitor, and Immune Cells Respond Ex Vivo to SARS-CoV-2 Spike Protein.
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DOI：
10.1007/s12015-020-10056-z
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发表时间：
2021-03
影响因子：
4.8
通讯作者：
Broxmeyer HE
中科院分区：
文献类型：
--
作者：
Ropa J;Cooper S;Capitano ML;Van't Hof W;Broxmeyer HE
尽管有证据表明SARS-CoV-2感染是系统性的，但人们对SARS-CoV-2感染或暴露对许多宿主细胞类型（包括原始和成熟造血细胞）的影响知之甚少。造血系统负责产生防御病毒感染的免疫细胞，并且是用于造血细胞移植（HCT）以治疗血液病的造血干细胞（HSC）和祖细胞（HPC）的来源，因此强烈需要了解暴露于病毒如何影响造血细胞功能。我们检测了ACE 2在脐带血来源的HSC/HPC和外周血来源的免疫细胞亚型中的表达，SARS-CoV-2 Spike（S）蛋白与ACE 2结合以促进病毒进入。ACE 2在少量免疫细胞、大量HPC和高达65%的严格定义的HSC中表达。我们还研究了离体暴露于SARS-CoV-2S蛋白的HSC/HPC和免疫细胞的影响。当与S蛋白一起生长时，HSC和HPC扩增效率较低，并且具有较低的功能性集落形成能力，而外周血单核细胞上调CD 14表达，并且在大小和粒度上显示出明显的变化。这些效应是由重组S蛋白单独诱导的，而不是感染性病毒颗粒，这表明简单暴露于SARS-CoV-2可能通过S蛋白与细胞的相互作用影响HSC/HPC和免疫细胞，无论它们是否可以被感染。这些数据对SARS-CoV-2和HCT的免疫应答具有影响。·人类HSC、HPC和免疫细胞在细胞表面表达ACE 2，使它们可能对SARS-CoV-2感染易感。· SARS-CoV-2 S蛋白与ACE 2结合，诱导人HPC的殖民地形成能力缺陷，并抑制HSC/HPC亚群的离体扩增。这些作用可以通过SARS-CoV-2靶向抗体、重组人ACE 2或血管紧张素1 -7治疗至少部分中和。· S蛋白还在离体外周血来源的单核细胞中诱导异常形态学变化。·因此，SARS-CoV-2病毒可能以许多不同的方式影响功能性造血系统，这对COVID-19的血液学表现（即血小板减少症和淋巴细胞减少症），免疫反应和COVID-19时代的造血干细胞移植具有重要意义。本文的在线版本（10.1007/s12015-020-10056-z）包含补充材料，可供授权用户使用。
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. • Human HSCs, HPCs, and immune cells express ACE2 on the cell surface, making them potentially susceptible to SARS-CoV-2 infection. • SARS-CoV-2 S protein, which binds to ACE2, induces defects in the colony forming capacity of human HPC and inhibits the expansion of HSC/HPC subpopulations ex vivo. These effects can be at least partially neutralized by treatment with SARS-CoV-2 targeting antibody, recombinant human ACE2, or Angiotensin1–7. • S protein also induces aberrant morphological changes in peripheral blood derived monocytes ex vivo. • Thus, there are many different manners in which SARS-CoV-2 virus may impact the functional hematopoietic system, which has important implications for hematological manifestations of COVID-19 (i.e. thrombocytopenia and lymphopenia), immune response, and hematopoietic stem cell transplant in the era of COVID-19. The online version of this article (10.1007/s12015-020-10056-z) contains supplementary material, which is available to authorized users.
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影响因子：
5.4
作者：
Heurich, Adeline;Hofmann-Winkler, Heike;Poehlmann, Stefan
通讯作者：
Poehlmann, Stefan
影响因子：
82.9
作者：
Guo B;Huang X;Lee MR;Lee SA;Broxmeyer HE
通讯作者：
Broxmeyer HE
DOI：
10.1073/pnas.0237086100
发表时间：
2003-01-21
影响因子：
11.1
作者：
Broxmeyer, HE;Srour, EF;Bodine, DM
通讯作者：
Bodine, DM
影响因子：
11.8
作者：
Banerjee, Arinjay;Nasir, Jalees A.;Mubareka, Samira
通讯作者：
Mubareka, Samira
影响因子：
168.9
作者：
Huang, Chaolin;Wang, Yeming;Cao, Bin
通讯作者：
Cao, Bin