Defining epithelial cell dynamics and lineage relationships in the developing lacrimal gland

Author:

Farmer D'Juan1,Nathan Sara2,Finley Jennifer2,Yu Kevin Shengyang3,Emmerson Elaine2,Byrnes Lauren1,Sneddon Julie1,McManus Michael1,Tward Aaron3,Knox Sarah2ORCID

Affiliation:

1. Diabetes Center at the University of California, San Francisco, CA, 94143, USA

2. Department of Cell and Tissue Biology at the University of California, San Francisco, CA, 94143, USA

3. Department of Otolaryngology at the University of California, San Francisco, CA, 94143, USA

Abstract

The tear producing lacrimal gland is a tubular organ that protects and lubricates the ocular surface. While the lacrimal gland possesses many features that make it an excellent model to understand tubulogenesis, the cell types and lineage relationships that drive lacrimal gland formation are unclear. Using single cell sequencing and other molecular tools, we reveal novel cell identities and epithelial lineage dynamics that underlie lacrimal gland development. We show that the lacrimal gland from its earliest developmental stages is composed of multiple subpopulations of immune, epithelial, and mesenchymal cell lineages. The epithelial lineage exhibits the most substantiative cellular changes, transitioning through a series of unique transcriptional states to become terminally differentiated acinar, ductal and myoepithelial cells. Furthermore, lineage tracing in postnatal and adult glands provides the first direct evidence of unipotent KRT5+ epithelial cells in the lacrimal gland. Finally, we show conservation of developmental markers between the developing mouse and human lacrimal gland, supporting the use of mice to understand human development. Together, our data reveal critical features of lacrimal gland development that have broad implications for understanding epithelial organogenesis.

Funder

National Eye Institute

National Cancer Institute

Publisher

The Company of Biologists

Subject

Developmental Biology,Molecular Biology

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