Multidimensional Proteomic Approach of Endothelial Progenitors Demonstrate Expression of KDR Restricted to CD19 Cells.
Multidimensional Proteomic Approach of Endothelial Progenitors Demonstrate Expression of KDR Restricted to CD19 Cells.
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DOI：
10.1007/s12015-020-10062-1
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发表时间：
2021-04
影响因子：
4.8
通讯作者：
Smadja DM
中科院分区：
文献类型：
--
作者：
Guerin CL;Guyonnet L;Goudot G;Revets D;Konstantinou M;Chipont A;Chocron R;Blandinieres A;Khider L;Rancic J;Peronino C;Debuc B;Cras A;Knosp C;Latremouille C;Capel A;Ollert M;Diehl JL;Jansen P;Planquette B;Sanchez O;Gaussem P;Mirault T;Carpentier A;Gendron N;Smadja DM
内皮祖细胞（EPC）参与血管生成和心血管疾病。然而，循环 EPC 的表型仍然难以捉摸，但它们通常被描述为 CD34+KDR+。该研究的目的是通过强大的多维单细胞互补细胞计数方法（质量、成像和流式）广泛表征两个心血管疾病患者群体中循环潜在血管生成干细胞候选物的特征。我们在一名患者的生物假体全人工心脏植入前后鉴定了候选细胞，并通过质量细胞计数在健康的外周血和脐带血中证实了结果。我们还对 10 名具有不同 COVID-19 严重程度的患者的候选细胞进行了量化。 C-TAH 植入和关键阶段的 COVID-19 都会诱导外周血中循环 CD34+ 和 CD19+ 亚群的重新分布。 C-TAH 植入后，循环 CD34+ 祖细胞表达 c-Kit 干细胞标记，同时特定亚群 CD34+CD133−/+CD45−/dimc-Kit+KDR− 被动员。 KDR 仅由循环中的 CD19+ B 淋巴细胞和 CD14+ 单核细胞亚群表达。我们通过质谱流式分析证实了健康外周血和脐带血中 CD19+ 上的 KDR 表达，以及 VE-钙粘蛋白的表达，证实了 CD34+ 亚型上不存在内皮谱系标记。在 COVID-19 中，无论 CD133 或 CD45 表达如何，在中度和危重 COVID-19 患者中都观察到 CD34+c-Kit+KDR− 细胞的显着动员。为了更好地评估EPC表型，我们对脐带血中未成熟的CD34+KDR+细胞进行了成像流式细胞术测量，结果表明，在消除非循环事件后，这些细胞都是CD19+。在 COVID-19 期间，无论 CD34 表达如何，在中度和危重 COVID-19 患者中观察到每百万个 CD45+ 细胞中 CD19+KDR+ 显着动员。 CD34+c-Kit+ 细胞在此处描述的两种心血管疾病中均被动员。外周血中的 KDR 细胞是 CD19 阳性细胞，不是典型的血管生成干细胞和/或祖细胞。对 c-Kit 和 KDR 表达细胞的更好评估将导致循环内皮祖细胞的重新定义。中央插图图。内皮祖细胞的多维蛋白质组学方法证明 KDR 的表达仅限于 CD19 细胞。内皮祖细胞（EPC）与心血管疾病有关，但其表型仍然难以捉摸。我们在生物假体全人工心脏植入后和 COVID-19 期间通过多维单细胞互补细胞计数方法进行深入表征，阐明了 EPC 表型。我们展示了两种情况下循环 CD34+ 和 CD19+ 亚群的重新分布。未成熟细胞群均不表达 KDR。动员 CD34+ 表达 c-Kit。成像流式细胞术证明CD34+KDR+细胞在消除非循环事件后全部为CD19+。我们的结果提出了循环 EPC 的新定义，并强调 CD19 细胞在心血管疾病中的参与。图解摘要 在线版本包含可在 10.1007/s12015-020-10062-1 获取的补充材料。
Endothelial progenitor cells (EPCs) are involved in vasculogenesis and cardiovascular diseases. However, the phenotype of circulating EPCs remains elusive but they are more often described as CD34+KDR+. The aim of the study was to extensively characterize circulating potential vasculogenic stem cell candidates in two populations of patients with cardiovascular disease by powerful multidimensional single cell complementary cytometric approaches (mass, imaging and flow). We identified cellular candidates in one patient before and after bioprosthetic total artificial heart implantation and results were confirmed in healthy peripheral and cord blood by mass cytometry. We also quantified cellular candidates in 10 patients with different COVID-19 severity. Both C-TAH implantation and COVID-19 at critical stage induce a redistribution of circulating CD34+ and CD19+ sub-populations in peripheral blood. After C-TAH implantation, circulating CD34+ progenitor cells expressed c-Kit stem marker while specific subsets CD34+CD133−/+CD45−/dimc-Kit+KDR− were mobilized. KDR was only expressed by CD19+ B-lymphocytes and CD14+ monocytes subpopulations in circulation. We confirmed by mass cytometry this KDR expression on CD19+ in healthy peripheral and cord blood, also with a VE-cadherin expression, confirming absence of endothelial lineage marker on CD34+ subtypes. In COVID-19, a significant mobilization of CD34+c-Kit+KDR− cells was observed between moderate and critical COVID-19 patients regardless CD133 or CD45 expression. In order to better evaluate EPC phenotype, we performed imaging flow cytometry measurements of immature CD34+KDR+ cells in cord blood and showed that, after elimination of non-circular events, those cells were all CD19+. During COVID-19, a significant mobilization of CD19+KDR+ per million of CD45+ cells was observed between moderate and critical COVID-19 patients regardless of CD34 expression. CD34+c-Kit+ cells are mobilized in both cardiovascular disease described here. KDR cells in peripheral blood are CD19 positive cells and are not classic vasculogenic stem and/or progenitor cells. A better evaluation of c-Kit and KDR expressing cells will lead to the redefinition of circulating endothelial progenitors. Central illustration figure. Multidimensional proteomic approach of endothelial progenitors demonstrate expression of KDR restricted to CD19 cells. Endothelial progenitor cells (EPCs) are involved in cardiovascular diseases, however their phenotype remains elusive. We elucidated here EPCs phenotype by a deep characterization by multidimensional single cell complementary cytometric approaches after Bioprosthetic total artificial heart implantation and during COVID-19. We showed a redistribution of circulating CD34+ and CD19+ sub-populations in both situations. None of the immature cell population expresses KDR. Mobilized CD34+ expressed c-Kit. Imaging flow cytometry demonstrated that CD34+KDR+ cells, after elimination of non-circular events, are all CD19+. Our results suggest a new definition of circulating EPCs and emphasize involvement of CD19 cells in cardiovascular disease. Graphical abstract The online version contains supplementary material available at 10.1007/s12015-020-10062-1.
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影响因子：
16.8
作者：
Bendall SC;Nolan GP;Roederer M;Chattopadhyay PK
通讯作者：
Chattopadhyay PK
影响因子：
8.1
作者：
Diehl, J-L;Peron, N.;Smadja, D. M.
通讯作者：
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作者：
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通讯作者：
Jonigk, Danny
影响因子：
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作者：
Mauge，Laetitia;Sabatier，Florence;Smadja，David M.
通讯作者：
Smadja，David M.
影响因子：
20.1
作者：
Rigato, Mauro;Avogaro, Angelo;Fadini, Gian Paolo
通讯作者：
Fadini, Gian Paolo