Transcriptomic profiling of Schlemm's canal cells reveals a lymphatic-biased identity and three major cell states.

Autor:	Balasubramanian R; Department of Ophthalmology, Columbia University Irving Medical Center, New York, United States., Kizhatil K; Department of Ophthalmology and Visual Sciences, The Ohio State University Medical Center, Columbus, United States., Li T; Department of Molecular Biology and Genetics, Johns Hopkins University, Baltimore, United States., Tolman N; Department of Ophthalmology, Columbia University Irving Medical Center, New York, United States.; Graduate School of Biomedical Sciences, Tufts University School of Medicine, Boston, United States., Bhandari A; Department of Ophthalmology, Columbia University Irving Medical Center, New York, United States.; Neuroscience Graduate Program, University of Utah, Salt Lake City, United States., Clark G; Department of Ophthalmology and Visual Sciences, The Ohio State University Medical Center, Columbus, United States., Bupp-Chickering V; Department of Ophthalmology, Columbia University Irving Medical Center, New York, United States., Kelly RA; Department of Ophthalmology, Duke University, Durham, United States., Zhou S; Department of Ophthalmology, Columbia University Irving Medical Center, New York, United States.; SUNY Downstate Health Sciences University, New York, United States., Peregrin J; Department of Ophthalmology, Columbia University Irving Medical Center, New York, United States., Simón M; Department of Ophthalmology, Columbia University Irving Medical Center, New York, United States., Montgomery C; Department of Ophthalmology, Columbia University Irving Medical Center, New York, United States., Stamer WD; Department of Ophthalmology, Duke University, Durham, United States., Qian J; Department of Ophthalmology, Johns Hopkins School of Medicine, Baltimore, United States., John SWM; Zuckerman Mind Brain Behavior Institute, Columbia University, New York, United States.
Jazyk:	angličtina
Zdroj:	ELife [Elife] 2024 Oct 18; Vol. 13. Date of Electronic Publication: 2024 Oct 18.
DOI:	10.7554/eLife.96459
Abstrakt:	Schlemm's canal (SC) is central in intraocular pressure regulation but requires much characterization. It has distinct inner and outer walls, each composed of Schlemm's canal endothelial cells (SECs) with different morphologies and functions. Recent transcriptomic studies of the anterior segment added important knowledge, but were limited in power by SEC numbers or did not focus on SC. To gain a more comprehensive understanding of SC biology, we performed bulk RNA sequencing on C57BL/6 J SC, blood vessel, and lymphatic endothelial cells from limbal tissue (~4,500 SECs). We also analyzed mouse limbal tissues by single-cell and single-nucleus RNA sequencing (C57BL/6 J and 129/Sj strains), successfully sequencing 903 individual SECs. Together, these datasets confirm that SC has molecular characteristics of both blood and lymphatic endothelia with a lymphatic phenotype predominating. SECs are enriched in pathways that regulate cell-cell junction formation pointing to the importance of junctions in determining SC fluid permeability. Importantly, and for the first time, our analyses characterize three molecular classes of SECs, molecularly distinguishing inner wall from outer wall SECs and discovering two inner wall cell states that likely result from local environmental differences. Further, and based on ligand and receptor expression patterns, we document key interactions between SECs and cells of the adjacent trabecular meshwork (TM) drainage tissue. Also, we present cell type expression for a collection of human glaucoma genes. These data provide a new molecular foundation that will enable the functional dissection of key homeostatic processes mediated by SECs as well as the development of new glaucoma therapeutics. Competing Interests: RB, KK, TL, NT, AB, GC, VB, RK, SZ, JP, MS, CM, WS, JQ, SJ No competing interests declared (© 2024, Balasubramanian, Kizhatil et al.)
Databáze:	MEDLINE
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