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

D'Juan T Farmer, Sara Nathan, Jennifer K Finley, Kevin Shengyang Yu, Elaine Emmerson, Lauren E Byrnes, Julie B Sneddon, Michael T McManus, Aaron D Tward, Sarah M Knox

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

The tear-producing lacrimal gland is a tubular organ that protects and lubricates the ocular surface. The lacrimal gland possesses many features that make it an excellent model in which to investigate tubulogenesis, but 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 substantial 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 crucial features of lacrimal gland development that have broad implications for understanding epithelial organogenesis.

Original languageEnglish
Pages (from-to)2517-2528
Number of pages12
JournalDevelopment
Volume144
Issue number13
Early online date2 Jun 2017
DOIs
Publication statusPublished - 4 Jul 2017

Keywords / Materials (for Non-textual outputs)

  • Acinar Cells
  • Animals
  • Biomarkers
  • Cell Lineage
  • Epithelial Cells
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation, Developmental
  • Humans
  • Lacrimal Apparatus
  • Mice
  • Phenotype
  • Sequence Analysis, RNA
  • Single-Cell Analysis
  • Stem Cells
  • Journal Article
  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

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