PXD025629

PXD025629 is an original dataset announced via ProteomeXchange.

Title	SARS-CoV-2 infects human pancreatic β-cells and elicits β-cell impairment
Description	Emerging evidence points towards an intricate relationship between the pandemic coronavirus disease 2019 (COVID-19) and diabetes. While diabetes is associated with an increased risk of severe COVID-19, new-onset type 1 diabetes (T1D) has been observed in COVID-19 patients, convoluting diabetes as both a risk factor and consequence of COVID-19. Understanding the mechanistic relationship between COVID-19 and T1D is an urgent and critical public health challenge. One pressing question is whether insulin-producing pancreatic β-cells can be infected by SARS-CoV-2, as T1D is a direct consequence of β-cell depletion. Here, we find that the SARS-CoV-2 receptor, ACE2 and its related entry factors, TMPRSS2, NRP1, and TRFC, are expressed in β-cells, with the latter two selectively present within β-cells. We discover that SARS-CoV-2 has selective cellular tropism for human pancreatic β-cells both ex vivo and in patients with COVID-19. We demonstrate that SARS-CoV-2 infection lowers the abundance of insulin within the pancreas, attenuates glucose-stimulated insulin secretion, and induces β-cell apoptosis. Finally, phosphoproteomic and pathway analysis suggests a SARS-CoV-2 stimulated signature for induction of apoptosis-associated signaling pathways in β-cells, similar to that seen in T1D. Taken together, our study demonstrates that SARS- CoV-2 can directly cause pancreatic islet impairment by killing β-cells, providing a mechanistic explanation for why T1D develops in COVID-19 patients.
HostingRepository	PRIDE
AnnounceDate	2021-07-24
AnnouncementXML	Submission_2021-07-24_11:47:04.682.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD025629
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Janos Demeter
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090; scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue; acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	timsTOF Pro

Revision	Datetime	Status	ChangeLog Entry
0	2021-04-26 00:59:03	ID requested
⏵ 1	2021-07-24 11:47:05	announced

Wu CT, Lidsky PV, Xiao Y, Lee IT, Cheng R, Nakayama T, Jiang S, Demeter J, Bevacqua RJ, Chang CA, Whitener RL, Stalder AK, Zhu B, Chen H, Goltsev Y, Tzankov A, Nayak JV, Nolan GP, Matter MS, Andino R, Jackson PK, cell impairment. Cell Metab, 33(8):1565-1576.e5(2021) [pubmed]

submitter keyword: SARS-CoV-2, human, pancreas, beta-cells

Jackson, Peter, K.
contact affiliation	Baxter Laboratory for Stem Cell Biology Department of Microbiology & Immunology Stanford University School of Medicine 269 Campus Drive CCSR 3205b Stanford, CA 94305-5175 USA
contact email	pjackson@stanford.edu
lab head
Janos Demeter
contact affiliation	Stanford University
contact email	jdemeter@stanford.edu
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2021/07/PXD025629

PRIDE project URI

• PRIDE
  1. PXD025629
     1. Label: PRIDE project
     2. Name: SARS-CoV-2 infects human pancreatic β-cells and elicits β-cell impairment