PXD040918-2

PXD040918 is an original dataset announced via ProteomeXchange.

Title	Human limbal epithelial cell-derived exosomes cargo profile and their regulatory roles in limbal stromal cells in diabetic and non-diabetic cornea
Description	Limbal stem cells including epithelial and stromal/Mesenchymal stem cells that contribute to sustained corneal homeostasis, maintain their ability to act as self-renewal progenitor cells by virtue of their limbal niche and intercellular communication. Extracellular vehicles (EVs), including exosomes (Exos), are important paracrine mediators through their cargo transfer for intercellular communication in various stem cell niches. Previously we have shown the differential cargos and regulatory roles of limbal stromal cell (LSC)-derived Exos, in limbal epithelial cells (LEC) in normal (N) and diabetic (DM) limbal niche. In the present study, to have a comprehensive knowledge of reciprocal LEC-LSC crosstalk, we investigated the proteomics and miRNA profile of exosomes derived from LEC and their regulatory roles in LSC in N and DM limbus. Our study showed wound healing and proliferation rates in primary N-LSC were significantly enhanced upon treatment by normal LEC-derived Exos (N-Exos), but not by diabetic Exos (DM-Exos). Further, N-Exos treated LSC showed downregulation of keratocyte markers, ALDH3A1 and lumican, but not keratocan, and upregulation of MSC markers, CD105, CD90, and CD73 compared to the DM-Exos treated LSC. Using next generation sequencing (NGS) and proteomics analysis, we revealed some miRNAs and proteins in the Exos that affect the cellular crosstalk and the function of the cornea. We also documented differences in DM vs. normal LEC-derived Exo’s cargos. Overall, DM-Exos have less effect on LSC proliferation, wound healing, and stem cell maintenance than N-Exos, likely by transferring their cargo proteins and/or regulatory miRNAs targeting cell cycle, ERK/MAPK, TGF-β, EMT, PI3K-Akt-mTOR signaling molecules. This suggests that the small RNA and protein cargo differences in DM vs. N LEC-derived Exos could contribute to the disease state. Our study revealed a complex contribution of Exos to health and diabetic state of corneal homeostasis and suggests the potential of EV therapeutics for diabetic cornea regenerative medicine
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_06:07:09.712.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Aleksandr Stotland
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2023-03-16 12:55:27	ID requested
1	2023-10-23 09:31:05	announced
⏵ 2	2024-10-22 06:07:10	announced	2024-10-22: Updated project metadata.

Dataset with its publication pending

submitter keyword: Diabetes, Cornea,Exosomes

Mehrnoosh Saghizadeh
contact affiliation	The Smidt Heart Institute, Cedars Sinai Medical Center Cedars-Sinai Medical Center 6David Geffen School of Medicine at UCLA
contact email	mehrnoosh.ghiam@cshs.org
lab head
Aleksandr Stotland
contact affiliation	Cedars-Sinai Medical Center
contact email	aleksandr.stotland@cshs.org
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD040918
     1. Label: PRIDE project
     2. Name: Human limbal epithelial cell-derived exosomes cargo profile and their regulatory roles in limbal stromal cells in diabetic and non-diabetic cornea