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

Marie Bannier-Hélaouët, Yorick Post, Jeroen Korving, Marc Trani Bustos, Helmuth Gehart, Harry Begthel, Yotam E Bar-Ephraim, Jelte van der Vaart, Rachel Kalmann, Saskia M Imhoff, Hans Clevers

Research output: Contribution to journal/periodicalArticleScientificpeer-review

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.

Original languageEnglish
Pages (from-to)1221-1232.e7
JournalCell Stem Cell
Volume28
Issue number7
DOIs
Publication statusPublished - 01 Jul 2021

Keywords

  • Animals
  • Dry Eye Syndromes
  • Humans
  • Lacrimal Apparatus
  • Mice
  • Organoids
  • Stem Cells
  • Tears

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