SARS-CoV-2 Cell Entry Factors ACE2 and TMPRSS2 Are Expressed in the Microvasculature and Ducts of Human Pancreas but Are Not Enriched in β Cells

HPAP Consortium

doi:10.1016/j.cmet.2020.11.006

SARS-CoV-2 Cell Entry Factors ACE2 and TMPRSS2 Are Expressed in the Microvasculature and Ducts of Human Pancreas but Are Not Enriched in β Cells

HPAP Consortium

Pediatrics

Research output: Contribution to journal › Article › peer-review

145 Scopus citations

Abstract

Coate et al. examined expression of canonical SARS-CoV-2 entry proteins ACE2 and TMPRSS2 in the human pancreas and report ACE2 expression in the microvasculature, including islet pericytes, whereas both ACE2 and TMPRSS2 are expressed in some ducts. Conversely, neither protein is detected in β cells, arguing against direct β cell viral infection in vivo.

Original language	English (US)
Pages (from-to)	1028-1040.e4
Journal	Cell Metabolism
Volume	32
Issue number	6
DOIs	https://doi.org/10.1016/j.cmet.2020.11.006
State	Published - Dec 1 2020

Funding

We are especially thankful to organ donors and their families. This research was supported by funding provided by the National Institute of Diabetes and Digestive and Kidney Diseases; the Human Islet Research Network (HIRN, RRID: SCR_014393, https://hirnetwork.org; DK112232, DK123716, U01DK123594, DK104211, DK108120); DK106755, DK117147, DK117147-01A1S1, DK111757, DK112217, and DK20593; and the Functional Genomics Core of DK19525. This manuscript used data acquired from and available at the Human Pancreas Analysis Program (HPAP, RRID: SCR_016202) Database (https://hpap.pmacs.upenn.edu), a HIRN consortium. This work was also supported by grants from the Doris Duke Charitable Foundation (DDCF 4043516256), Human Islet Research Network New Investigator Pilot Award (UC4 DK104162), JDRF, the Leona M. and Harry B. Helmsley Charitable Trust, and the Department of Veterans Affairs (BX000666). Human pancreatic islets were provided by the NIDDK-funded Integrated Islet Distribution Program at the City of Hope (NIH grant # 2UC4 DK098085; RRID: SCR_014387; https://iidp.coh.org). Human kidney sections were provided by Dr. Agnes B. Fogo at Vanderbilt University Medical Center. We thank the Vanderbilt University Medical Center Translational Pathology Shared Resource (supported by NCI/NIH Cancer Center Support Grant 2P30 CA068485-14 and the Vanderbilt Mouse Metabolic Phenotyping Center 5U24DK059637-13). We also thank Amber M. Bradley for technical assistance. The graphical abstract was created with https://biorender.com/. K.C.C. J.C. M.B. and A.C.P. designed the experiments. K.C.C. J.C. M.B. and A.C.P. wrote the manuscript. K.C.C. J.C. S.S. W.W. L.M.G. J.A. M.E.K. M.F. A.M. C.D. D.C.S. R.B. R.J. R.S. K.H.K. G.V. M.B. and A.C.P. performed experiments or analyzed the data. All authors reviewed and edited the final manuscript. The authors declare no competing interests. We are especially thankful to organ donors and their families. This research was supported by funding provided by the National Institute of Diabetes and Digestive and Kidney Diseases ; the Human Islet Research Network (HIRN, RRID: SCR_014393 , https://hirnetwork.org ; DK112232 , DK123716 , U01DK123594 , DK104211 , DK108120 ); DK106755 , DK117147 , DK117147-01A1S1 , DK111757 , DK112217 , and DK20593 ; and the Functional Genomics Core of DK19525 . This manuscript used data acquired from and available at the Human Pancreas Analysis Program (HPAP, RRID: SCR_016202 ) Database ( https://hpap.pmacs.upenn.edu ), a HIRN consortium. This work was also supported by grants from the Doris Duke Charitable Foundation (DDCF 4043516256 ), Human Islet Research Network New Investigator Pilot Award ( UC4 DK104162 ), JDRF , the Leona M. and Harry B. Helmsley Charitable Trust , and the Department of Veterans Affairs ( BX000666 ). Human pancreatic islets were provided by the NIDDK-funded Integrated Islet Distribution Program at the City of Hope ( NIH grant # 2UC4 DK098085 ; RRID: SCR_014387 ; https://iidp.coh.org ). Human kidney sections were provided by Dr. Agnes B. Fogo at Vanderbilt University Medical Center. We thank the Vanderbilt University Medical Center Translational Pathology Shared Resource (supported by NCI/NIH Cancer Center Support Grant 2P30 CA068485-14 and the Vanderbilt Mouse Metabolic Phenotyping Center 5U24DK059637-13 ). We also thank Amber M. Bradley for technical assistance. The graphical abstract was created with https://biorender.com/ .

Keywords

ACE2
COVID-19
SARS-CoV-2
TMPRSS2
beta cell
duct
islet
microvasculature
pancreas
pericyte

ASJC Scopus subject areas

Physiology
Molecular Biology
Cell Biology

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10.1016/j.cmet.2020.11.006

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title = "SARS-CoV-2 Cell Entry Factors ACE2 and TMPRSS2 Are Expressed in the Microvasculature and Ducts of Human Pancreas but Are Not Enriched in β Cells",

abstract = "Coate et al. examined expression of canonical SARS-CoV-2 entry proteins ACE2 and TMPRSS2 in the human pancreas and report ACE2 expression in the microvasculature, including islet pericytes, whereas both ACE2 and TMPRSS2 are expressed in some ducts. Conversely, neither protein is detected in β cells, arguing against direct β cell viral infection in vivo.",

keywords = "ACE2, COVID-19, SARS-CoV-2, TMPRSS2, beta cell, duct, islet, microvasculature, pancreas, pericyte",

author = "{HPAP Consortium} and Coate, {Katie C.} and Jeeyeon Cha and Shristi Shrestha and Wenliang Wang and Gon{\c c}alves, {Luciana Mateus} and Joana Alma{\c c}a and Kapp, {Meghan E.} and Maria Fasolino and Ashleigh Morgan and Chunhua Dai and Saunders, {Diane C.} and Rita Bottino and Radhika Aramandla and Regina Jenkins and Roland Stein and Kaestner, {Klaus H.} and Golnaz Vahedi and Marcela Brissova and Powers, {Alvin C.}",

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year = "2020",

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doi = "10.1016/j.cmet.2020.11.006",

language = "English (US)",

volume = "32",

pages = "1028--1040.e4",

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AU - HPAP Consortium

AU - Coate, Katie C.

AU - Cha, Jeeyeon

AU - Shrestha, Shristi

AU - Wang, Wenliang

AU - Gonçalves, Luciana Mateus

AU - Almaça, Joana

AU - Kapp, Meghan E.

AU - Fasolino, Maria

AU - Morgan, Ashleigh

AU - Dai, Chunhua

AU - Saunders, Diane C.

AU - Bottino, Rita

AU - Aramandla, Radhika

AU - Jenkins, Regina

AU - Stein, Roland

AU - Kaestner, Klaus H.

AU - Vahedi, Golnaz

AU - Brissova, Marcela

AU - Powers, Alvin C.

PY - 2020/12/1

Y1 - 2020/12/1

N2 - Coate et al. examined expression of canonical SARS-CoV-2 entry proteins ACE2 and TMPRSS2 in the human pancreas and report ACE2 expression in the microvasculature, including islet pericytes, whereas both ACE2 and TMPRSS2 are expressed in some ducts. Conversely, neither protein is detected in β cells, arguing against direct β cell viral infection in vivo.

AB - Coate et al. examined expression of canonical SARS-CoV-2 entry proteins ACE2 and TMPRSS2 in the human pancreas and report ACE2 expression in the microvasculature, including islet pericytes, whereas both ACE2 and TMPRSS2 are expressed in some ducts. Conversely, neither protein is detected in β cells, arguing against direct β cell viral infection in vivo.

KW - ACE2

KW - COVID-19

KW - SARS-CoV-2

KW - TMPRSS2

KW - beta cell

KW - duct

KW - islet

KW - microvasculature

KW - pancreas

KW - pericyte

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JO - Cell Metabolism

JF - Cell Metabolism

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SARS-CoV-2 Cell Entry Factors ACE2 and TMPRSS2 Are Expressed in the Microvasculature and Ducts of Human Pancreas but Are Not Enriched in β Cells

Abstract

Funding

Keywords

ASJC Scopus subject areas

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