한빛사 논문
Katie C. Coate1,10, Jeeyeon Cha1,10, Shristi Shrestha1, Wenliang Wang2, Luciana Mateus Gonçalves3, Joana Almaça3, Meghan E. Kapp4, Maria Fasolino2, Ashleigh Morgan2, Chunhua Dai1, Diane C. Saunders1, Rita Bottino6,7, Radhika Aramandla1, Regina Jenkins1, Roland Stein8, Klaus H. Kaestner2, Golnaz Vahedi2, HPAP Consortium9, Marcela Brissova1,*, Alvin C. Powers1,5,8,11,*
1Division of Diabetes, Endocrinology and Metabolism, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, USA
2Department of Genetics and Institute for Diabetes, Obesity, and Metabolism, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA
3Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, University of Miami Miller School of Medicine, Miami, FL 33136, USA
4Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232, USA
5VA Tennessee Valley Healthcare System, Nashville, TN 37212, USA
6Institute of Cellular Therapeutics, Allegheny Health Network, Pittsburgh, PA 15212, USA
7Imagine Pharma, Devon, PA 19333, USA
8Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, TN 37232, USA
9The Human Pancreas Analysis Program
10These authors contributed equally
11Lead Contact
*Corresponding author
Abstract
Isolated reports of new-onset diabetes in individuals with COVID-19 have led to the hypothesis that SARS-CoV-2 is directly cytotoxic to pancreatic islet β cells. This would require binding and entry of SARS-CoV-2 into β cells via co-expression of its canonical cell entry factors, angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2); however, their expression in human pancreas has not been clearly defined. We analyzed six transcriptional datasets of primary human islet cells and found that ACE2 and TMPRSS2 were not co-expressed in single β cells. In pancreatic sections, ACE2 and TMPRSS2 protein was not detected in β cells from donors with and without diabetes. Instead, ACE2 protein was expressed in islet and exocrine tissue microvasculature and in a subset of pancreatic ducts, whereas TMPRSS2 protein was restricted to ductal cells. These findings reduce the likelihood that SARS-CoV-2 directly infects β cells in vivo through ACE2 and TMPRSS2.
Keywords : SARS-CoV-2, COVID-19, ACE2, TMPRSS2, islet, beta cell, pericyte, microvasculature, duct, pancreas
논문정보
관련 링크