Single-Cell Microwell Platform Reveals Circulating Neural Cells as a Clinical Indicator for Patients with Blood-Brain Barrier Breakdown

Central nervous system diseases commonly occur with the destruction of the blood-brain barrier. As a primary cause of morbidity and mortality, stroke remains unpredictable and lacks cellular biomarkers that accurately quantify its occurrence and development. Here, we identify NeuN+/CD45−/DAPI+ pheno...

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Main Authors: Yu Zhang, Antony R. Warden, Khan Zara Ahmad, Yanlei Liu, Xijun He, Minqiao Zheng, Xinlong Huo, Xiao Zhi, Yuqing Ke, Hongxia Li, Sijia Yan, Wenqiong Su, Deng Cai, Xianting Ding
Format: Article
Language:English
Published: American Association for the Advancement of Science 2021-01-01
Series:Research
Online Access:http://dx.doi.org/10.34133/2021/9873545
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author Yu Zhang
Antony R. Warden
Khan Zara Ahmad
Yanlei Liu
Xijun He
Minqiao Zheng
Xinlong Huo
Xiao Zhi
Yuqing Ke
Hongxia Li
Sijia Yan
Wenqiong Su
Deng Cai
Xianting Ding
spellingShingle Yu Zhang
Antony R. Warden
Khan Zara Ahmad
Yanlei Liu
Xijun He
Minqiao Zheng
Xinlong Huo
Xiao Zhi
Yuqing Ke
Hongxia Li
Sijia Yan
Wenqiong Su
Deng Cai
Xianting Ding
Single-Cell Microwell Platform Reveals Circulating Neural Cells as a Clinical Indicator for Patients with Blood-Brain Barrier Breakdown
Research
author_facet Yu Zhang
Antony R. Warden
Khan Zara Ahmad
Yanlei Liu
Xijun He
Minqiao Zheng
Xinlong Huo
Xiao Zhi
Yuqing Ke
Hongxia Li
Sijia Yan
Wenqiong Su
Deng Cai
Xianting Ding
author_sort Yu Zhang
title Single-Cell Microwell Platform Reveals Circulating Neural Cells as a Clinical Indicator for Patients with Blood-Brain Barrier Breakdown
title_short Single-Cell Microwell Platform Reveals Circulating Neural Cells as a Clinical Indicator for Patients with Blood-Brain Barrier Breakdown
title_full Single-Cell Microwell Platform Reveals Circulating Neural Cells as a Clinical Indicator for Patients with Blood-Brain Barrier Breakdown
title_fullStr Single-Cell Microwell Platform Reveals Circulating Neural Cells as a Clinical Indicator for Patients with Blood-Brain Barrier Breakdown
title_full_unstemmed Single-Cell Microwell Platform Reveals Circulating Neural Cells as a Clinical Indicator for Patients with Blood-Brain Barrier Breakdown
title_sort single-cell microwell platform reveals circulating neural cells as a clinical indicator for patients with blood-brain barrier breakdown
publisher American Association for the Advancement of Science
series Research
issn 2639-5274
publishDate 2021-01-01
description Central nervous system diseases commonly occur with the destruction of the blood-brain barrier. As a primary cause of morbidity and mortality, stroke remains unpredictable and lacks cellular biomarkers that accurately quantify its occurrence and development. Here, we identify NeuN+/CD45−/DAPI+ phenotype nonblood cells in the peripheral blood of mice subjected to middle cerebral artery occlusion (MCAO) and stroke patients. Since NeuN is a specific marker of neural cells, we term these newly identified cells as circulating neural cells (CNCs). We find that the enumeration of CNCs in the blood is significantly associated with the severity of brain damage in MCAO mice (p<0.05). Meanwhile, the number of CNCs is significantly higher in stroke patients than in negative subjects (p<0.0001). These findings suggest that the amount of CNCs in circulation may serve as a clinical indicator for the real-time prognosis and progression monitor of the occurrence and development of ischemic stroke and other nervous system disease.
url http://dx.doi.org/10.34133/2021/9873545
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spelling doaj-49286a811ffe467f9f181fe33fd447ea2021-07-26T08:39:20ZengAmerican Association for the Advancement of ScienceResearch2639-52742021-01-01202110.34133/2021/9873545Single-Cell Microwell Platform Reveals Circulating Neural Cells as a Clinical Indicator for Patients with Blood-Brain Barrier BreakdownYu Zhang0Antony R. Warden1Khan Zara Ahmad2Yanlei Liu3Xijun He4Minqiao Zheng5Xinlong Huo6Xiao Zhi7Yuqing Ke8Hongxia Li9Sijia Yan10Wenqiong Su11Deng Cai12Xianting Ding13State Key Laboratory of Oncogenes and Related Genes,Institute for Personalized Medicine,School of Biomedical Engineering,Shanghai Jiao Tong University, 1954 Huashan Road, Shanghai 200030,ChinaState Key Laboratory of Oncogenes and Related Genes,Institute for Personalized Medicine,School of Biomedical Engineering,Shanghai Jiao Tong University, 1954 Huashan Road, Shanghai 200030,ChinaState Key Laboratory of Oncogenes and Related Genes,Institute for Personalized Medicine,School of Biomedical Engineering,Shanghai Jiao Tong University, 1954 Huashan Road, Shanghai 200030,ChinaShanghai Engineering Research Centre for Intelligent Diagnosis and Treatment Instrument,Department of Instrument Science and Engineering,School of Electronic Information and Electrical Engineering,Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240,ChinaDepartment of Neurosurgery,Wenling Hospital Affiliated to Wenzhou Medical University,Chuan’an Nan Road,Chengxi Subdistrict, Wenling, 317500 Zhejiang,ChinaCentral Laboratory,Wenling Hospital Affiliated to Wenzhou Medical University,Chuan’an Nan Road,Chengxi Subdistrict, Wenling, 317500 Zhejiang,ChinaDepartment of Neurology,Wenling Hospital Affiliated to Wenzhou Medical University,Chuan’an Nan Road,Chengxi Subdistrict, Wenling, 317500 Zhejiang,ChinaState Key Laboratory of Oncogenes and Related Genes,Institute for Personalized Medicine,School of Biomedical Engineering,Shanghai Jiao Tong University, 1954 Huashan Road, Shanghai 200030,ChinaState Key Laboratory of Oncogenes and Related Genes,Institute for Personalized Medicine,School of Biomedical Engineering,Shanghai Jiao Tong University, 1954 Huashan Road, Shanghai 200030,ChinaState Key Laboratory of Oncogenes and Related Genes,Institute for Personalized Medicine,School of Biomedical Engineering,Shanghai Jiao Tong University, 1954 Huashan Road, Shanghai 200030,ChinaState Key Laboratory of Oncogenes and Related Genes,Institute for Personalized Medicine,School of Biomedical Engineering,Shanghai Jiao Tong University, 1954 Huashan Road, Shanghai 200030,ChinaState Key Laboratory of Oncogenes and Related Genes,Institute for Personalized Medicine,School of Biomedical Engineering,Shanghai Jiao Tong University, 1954 Huashan Road, Shanghai 200030,ChinaDepartment of Thoracic Surgery,Shanghai Chest Hospital,Shanghai Jiao Tong University,241 West Huaihai Road, Shanghai 200030,ChinaState Key Laboratory of Oncogenes and Related Genes,Institute for Personalized Medicine,School of Biomedical Engineering,Shanghai Jiao Tong University, 1954 Huashan Road, Shanghai 200030,ChinaCentral nervous system diseases commonly occur with the destruction of the blood-brain barrier. As a primary cause of morbidity and mortality, stroke remains unpredictable and lacks cellular biomarkers that accurately quantify its occurrence and development. Here, we identify NeuN+/CD45−/DAPI+ phenotype nonblood cells in the peripheral blood of mice subjected to middle cerebral artery occlusion (MCAO) and stroke patients. Since NeuN is a specific marker of neural cells, we term these newly identified cells as circulating neural cells (CNCs). We find that the enumeration of CNCs in the blood is significantly associated with the severity of brain damage in MCAO mice (p<0.05). Meanwhile, the number of CNCs is significantly higher in stroke patients than in negative subjects (p<0.0001). These findings suggest that the amount of CNCs in circulation may serve as a clinical indicator for the real-time prognosis and progression monitor of the occurrence and development of ischemic stroke and other nervous system disease.http://dx.doi.org/10.34133/2021/9873545