Increased expression of hypoxia-induced factor 1α mRNA and its related genes in myeloid blood cells from critically ill COVID-19 patients.
Increased expression of hypoxia-induced factor 1α mRNA and its related genes in myeloid blood cells from critically ill COVID-19 patients.
复制标题
DOI：
10.1080/07853890.2020.1858234
复制
发表时间：
2021-12
影响因子：
4.4
通讯作者：
Mercado M
中科院分区：
文献类型：
--
作者：
Taniguchi-Ponciano K;Vadillo E;Mayani H;Gonzalez-Bonilla CR;Torres J;Majluf A;Flores-Padilla G;Wacher-Rodarte N;Galan JC;Ferat-Osorio E;Blanco-Favela F;Lopez-Macias C;Ferreira-Hermosillo A;Ramirez-Renteria C;Peña-Martínez E;Silva-Román G;Vela-Patiño S;Mata-Lozano C;Carvente-Garcia R;Basurto-Acevedo L;Saucedo R;Piña-Sanchez P;Chavez-Gonzalez A;Marrero-Rodríguez D;Mercado M
COVID-19导致4600万人感染，120多万人死亡。低氧血症是其主要临床表现之一，特别是在严重病例中。HIF 1 α是参与细胞对氧水平反应的主要转录因子。这种严重形式的COVID-19的免疫发病机制知之甚少。我们从5名重症COVID-19患者的白细胞中进行了scRNAseq，并表征了缺氧诱导因子1 α及其转录调控基因的表达。还对来自COVID-19支气管肺泡细胞的公开可用RNAseq数据进行了荟萃分析。重症COVID-19患者显示外周血细胞中向不成熟髓样特征转变，包括带状中性粒细胞、不成熟单核细胞、晚幼粒细胞、单核细胞-巨噬细胞、单核细胞样前体细胞和早幼粒细胞-髓细胞，以及成熟单核细胞和分叶中性粒细胞。可能是一种叫做紧急骨髓增生的生理反应的结果。这些细胞亚群和支气管肺泡细胞表达HIF 1 α及其与炎症（CXCL 8、CXCR 1、CXCR 2和CXCR 4）、病毒感应（TLR 2和TLR 4）和代谢（SLC 2A 3、PFKFB 3、PGK 1、GAPDH和SOD 2）相关的转录靶点。重症COVID-19患者出现紧急骨髓生成。HIF 1 α及其转录调控基因在未成熟的髓系细胞中表达，可作为分子靶点。HIF 1 α及其转录调控基因也在重症COVID-19患者的肺细胞中表达，这可能部分解释了缺氧相关事件。HIF 1 α在炎症、免疫代谢和TLR等事件中的上调和参与使其成为COVID-19严重程度的潜在分子标志物，有趣的是，它可能代表分子治疗的潜在靶点。
COVID-19 counts 46 million people infected and killed more than 1.2 million. Hypoxaemia is one of the main clinical manifestations, especially in severe cases. HIF1α is a master transcription factor involved in the cellular response to oxygen levels. The immunopathogenesis of this severe form of COVID-19 is poorly understood. We performed scRNAseq from leukocytes from five critically ill COVID-19 patients and characterized the expression of hypoxia-inducible factor1α and its transcriptionally regulated genes. Also performed metanalysis from the publicly available RNAseq data from COVID-19 bronchoalveolar cells. Critically-ill COVID-19 patients show a shift towards an immature myeloid profile in peripheral blood cells, including band neutrophils, immature monocytes, metamyelocytes, monocyte-macrophages, monocytoid precursors, and promyelocytes-myelocytes, together with mature monocytes and segmented neutrophils. May be the result of a physiological response known as emergency myelopoiesis. These cellular subsets and bronchoalveolar cells express HIF1α and their transcriptional targets related to inflammation (CXCL8, CXCR1, CXCR2, and CXCR4); virus sensing, (TLR2 and TLR4); and metabolism (SLC2A3, PFKFB3, PGK1, GAPDH and SOD2). Critically ill COVID-19 patients show emergency myelopoiesis. HIF1α and its transcriptionally regulated genes are expressed in immature myeloid cells which could serve as molecular targets. HIF1α and its transcriptionally regulated genes is also expressed in lung cells from critically ill COVID-19 patients which may partially explain the hypoxia related events. The up-regulation and participation of HIF1α in events such as inflammation, immunometabolism, and TLR make it a potential molecular marker for COVID-19 severity and, interestingly, could represent a potential target for molecular therapy.
登录
查看更多内容
影响因子：
12.4
作者：
Ha H;Debnath B;Neamati N
通讯作者：
Neamati N
影响因子：
168.9
作者：
Huang, Chaolin;Wang, Yeming;Cao, Bin
通讯作者：
Cao, Bin
影响因子：
4.2
作者：
Ishikawa, Tohru;Nakashiro, Koh-ichi;Hamakawa, Hiroyuki
通讯作者：
Hamakawa, Hiroyuki
影响因子：
12.7
作者：
Choudhury, Abhigyan;Mukherjee, Suprabhat
通讯作者：
Mukherjee, Suprabhat
影响因子：
8.8
作者：
Hoogendijk, Arie J.;Pourfarzad, Farzin;Kuijpers, Taco W.
通讯作者：
Kuijpers, Taco W.