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

TY - JOUR

T1 - Exploring the human lacrimal gland using organoids and single-cell sequencing

AU - Bannier-Hélaouët, Marie

AU - Post, Yorick

AU - Korving, Jeroen

AU - Trani Bustos, Marc

AU - Gehart, Helmuth

AU - Begthel, Harry

AU - Bar-Ephraim, Yotam E

AU - van der Vaart, Jelte

AU - Kalmann, Rachel

AU - Imhoff, Saskia M

AU - Clevers, Hans

N1 - Copyright © 2021 Elsevier Inc. All rights reserved.

PY - 2021/7/1

Y1 - 2021/7/1

N2 - 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.

AB - 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.

KW - Animals

KW - Dry Eye Syndromes

KW - Humans

KW - Lacrimal Apparatus

KW - Mice

KW - Organoids

KW - Stem Cells

KW - Tears

U2 - 10.1016/j.stem.2021.02.024

DO - 10.1016/j.stem.2021.02.024

M3 - Article

C2 - 33730555

SN - 1934-5909

VL - 28

SP - 1221-1232.e7

JO - Cell Stem Cell

JF - Cell Stem Cell

IS - 7

ER -