Non-neuronal expression of SARS-CoV-2 entry genes in the olfactory system suggests mechanisms underlying COVID-19-associated anosmia

被引：816

作者：

Brann, David H. ^{[1
]}

Tsukahara, Tatsuya ^{[1
]}

Weinreb, Caleb ^{[1
]}

Lipovsek, Marcela ^{[2
]}

Van den Berge, Koen ^{[3
,4
]}

Gong, Boying ^{[5
]}

Chance, Rebecca ^{[6
]}

Macaulay, Iain C. ^{[7
]}

Chou, Hsin-Jung ^{[6
]}

Fletcher, Russell B. ^{[6
,19
]}

Das, Diya ^{[6
,8
,20
]}

Street, Kelly ^{[9
,10
]}

de Bezieux, Hector Roux ^{[5
,11
]}

Choi, Yoon-Gi ^{[12
]}

Risso, Davide ^{[13
]}

Dudoit, Sandrine ^{[3
,5
]}

Purdom, Elizabeth ^{[3
]}

Mill, Jonathan ^{[14
]}

Hachem, Ralph Abi ^{[15
]}

Matsunami, Hiroaki ^{[16
]}

Logan, Darren W. ^{[17
]}

Goldstein, Bradley J. ^{[15
]}

Grubb, Matthew S. ^{[2
]}

Ngai, John ^{[6
,12
,18
,21
]}

Datta, Sandeep Robert ^{[1
]}

机构：

[1] Harvard Med Sch, Dept Neurobiol, Boston, MA 02115 USA

[2] Kings Coll London, Ctr Dev Neurobiol, Inst Psychiat Psychol & Neurosci IoPPN, London SE1 1UL, England

[3] Univ Calif Berkeley, Dept Stat, Berkeley, CA 94720 USA

[4] Univ Ghent, Dept Appl Math Comp Sci & Stat, Ghent, Belgium

[5] Univ Calif Berkeley, Sch Publ Hlth, Div Biostat, Berkeley, CA 94720 USA

[6] Univ Calif Berkeley, Dept Mol & Cell Biol, Berkeley, CA 94720 USA

[7] Earlham Inst, Norwich Res Pk, Norwich NR4 7UZ, Norfolk, England

[8] Univ Calif Berkeley, Berkeley Inst Data Sci, Berkeley, CA 94720 USA

[9] Dana Farber Canc Inst, Dept Data Sci, Boston, MA 02115 USA

[10] Harvard TH Chan Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA

[11] Univ Calif Berkeley, Ctr Computat Biol, Berkeley, CA 94720 USA

[12] Univ Calif Berkeley, QB3 Funct Genom Lab, Berkeley, CA 94720 USA

[13] Univ Padua, Dept Stat Sci, Padua, Italy

[14] Univ Exeter, Coll Med & Hlth, Med Sch, Exeter EX2 5DW, Devon, England

[15] Duke Univ, Dept Head & Neck Surg & Commun Sci, Sch Med, Durham, NC 27717 USA

[16] Duke Univ, Duke Inst Brain Sci, Dept Mol Genet & Microbiol, Dept Neuro Biol,Sch Med, Durham, NC 27710 USA

[17] Waltham Petcare Sci Inst, Melton Mowbray LE14 4RT, Leics, England

[18] Univ Calif Berkeley, Helen Wills Neurosci Inst, Berkeley, CA 94720 USA

[19] Surrozen Inc, San Francisco, CA 94080 USA

[20] Genentech Inc, San Francisco, CA 94080 USA

[21] NINDS, NIH, Bethesda, MD 20892 USA

来源：

SCIENCE ADVANCES | 2020年 / 6卷 / 31期

基金：

英国生物技术与生命科学研究理事会; 欧洲研究理事会; 英国医学研究理事会;

关键词：

RESPIRATORY SYNDROME CORONAVIRUS; MOUSE HEPATITIS-VIRUS; BULB LINE VARIANT; RNA-SEQ DATA; FUNCTIONAL RECEPTOR; SARS CORONAVIRUS; NEURON DIVERSITY; CELLS; EPITHELIUM; STEM;

D O I：

10.1126/sciadv.abc5801

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Altered olfactory function is a common symptom of COVID-19 (coronavirus disease 2019), but its etiology is unknown. A key question is whether SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2; CoV-2)-the causal agent in COVID-19-affects olfaction directly, by infecting olfactory sensory neurons or their targets in the olfactory bulb, or indirectly, by perturbing support cells. Bulk and single-cell RNA sequencing revealed that support and stem cells in the human and mouse olfactory epithelium and vascular pericytes in the mouse olfactory bulb express angiotensin-converting enzyme 2 (ACE2), which is essential for CoV-2 cell entry. In contrast, ACE2 was not detected in either olfactory sensory neurons or olfactory bulb neurons. Immunostaining confirmed these results and revealed pervasive expression of ACE2 protein in dorsally located olfactory epithelial sustentacular cells and mouse olfactory bulb pericytes. These findings suggest that CoV-2 infection of non-neuronal cell types leads to olfactory dysfunction in patients with COVID-19.

引用

页数：19

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