Exploring the human lacrimal gland using organoids and single-cell sequencing.

Cell Stem Cell

Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences (KNAW), University Medical Center Utrecht, 3584 CT Utrecht, the Netherlands; Oncode Institute, Hubrecht Institute, 3584 CT Utrecht, the Netherlands. Electronic address:

Published: July 2021

AI Article Synopsis

  • The lacrimal gland is crucial for keeping the eye lubricated and protected; problems in its fluid production can lead to dry eye syndrome, causing discomfort and eye damage.
  • This research establishes long-term 3D organoid cultures for both mouse and human lacrimal glands, which mimic key features of their natural structure and function.
  • The study identifies Pax6 as a critical gene for developing lacrimal gland cells and offers a detailed cell map of human lacrimal tissue, demonstrating that these organoids can replicate tear secretion and even successfully engraft in mouse models.

Article Abstract

The lacrimal gland is essential for lubrication and protection of the eye. Disruption of lacrimal fluid production, composition, or release results in dry eye, causing discomfort and damage to the ocular surface. Here, we describe the establishment of long-term 3D organoid culture conditions for mouse and human lacrimal gland. Organoids can be expanded over multiple months and recapitulate morphological and transcriptional features of lacrimal ducts. CRISPR-Cas9-mediated genome editing reveals the master regulator for eye development Pax6 to be required for differentiation of adult lacrimal gland cells. We address cellular heterogeneity of the lacrimal gland by providing a single-cell atlas of human lacrimal gland tissue and organoids. Finally, human lacrimal gland organoids phenocopy the process of tear secretion in response to neurotransmitters and can engraft and produce mature tear products upon orthotopic transplantation in mouse. Together, this study provides an experimental platform to study the (patho-)physiology of the lacrimal gland.

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Source
http://dx.doi.org/10.1016/j.stem.2021.02.024DOI Listing

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