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New Cell Markers in the Meibomian Gland Reveal All!

Review of “Biomarkers for Progenitor and Differentiated Epithelial Cells in the Human Meibomian Gland” from STEM CELLS Translational Medicine by Stuart P. Atkinson 

Meibum, an oily substance secreted by the meibomian glands (MGs) onto the ocular surface, acts to stabilize the tear film and prevent evaporation to preserve a healthy and functional ocular surface. MGs employ holocrine secretion, which entails the destruction of the meibum-containing epithelial cell (the meibocyte) [1]; therefore, holocrine secretion and proper MG function require the continual renewal of epithelial cells, possibly through the differentiation of so-far unidentified self-renewing stem/progenitor cells.

Researchers from the laboratory of Yang Liu (Harvard Medical School, Boston, USA) hypothesized that leucine‐rich repeats and immunoglobulin‐like domains protein 1 (Lrig1) [2, 3] and DNase2 [4, 5] may represent biomarkers for progenitors and differentiated cells in the human MG, respectively, based on studies of holocrine secretion of sebum from the sebaceous gland of the skin. In their new STEM CELLS Translational Medicine article, Xie et al. demonstrate how these biomarkers can aid our understanding of MG biology and support future clinical efforts to restore MG function or regenerate MGs following disease [6].

The authors processed human MG samples and discovered exclusive Lrig1 expression in the cytokeratin 14-expressing basal epithelial cells of the acinar periphery, a location where progenitor cells originate in the sebaceous gland, and exclusive DNase2 expression in the lipid‐laden lysosomes of differentiated epithelial cells of the MG central acinus. The authors also discovered the highly dynamic nature of marker expression over several consecutive proliferation/differentiation cycles in immortalized human MG epithelial cells (HMGECs) [7] - while proliferation stimulates and differentiation suppresses Lrig1 expression, proliferation suppresses and differentiation stimulates DNase2 expression. Overall, this suggests that HMGECs lie in a plastic state with the ability to transit between a progenitor and differentiated state.

The results of this new study not only support Lrig1 and DNase2 as biomarkers for progenitor and differentiated cells in the human MG, but also establish HMGECs an appropriate in vitro model, and suggest that primary HMGECs may play a prominent future role in MG regeneration in vivo.

For more on the meibomian gland and the search for markers for tissue-specific stem cells, stay tuned to the Stem Cells Portal!

References

  1. Knop E, Knop N, Millar T, et al., The international workshop on meibomian gland dysfunction: report of the subcommittee on anatomy, physiology, and pathophysiology of the meibomian gland. Investigative Ophthalmology & Visual Science 2011;52:1938-78.
  2. Jensen KB and Watt FM, Single-cell expression profiling of human epidermal stem and transit-amplifying cells: Lrig1 is a regulator of stem cell quiescence. Proceedings of the National Academy of Sciences 2006;103:11958-63.
  3. Jensen KB, Collins CA, Nascimento E, et al., Lrig1 expression defines a distinct multipotent stem cell population in mammalian epidermis. Cell Stem Cell 2009;4:427-39.
  4. Fischer H, Fumicz J, Rossiter H, et al., Holocrine Secretion of Sebum Is a Unique DNase2-Dependent Mode of Programmed Cell Death. Journal of Investigative Dermatology 2017;137:587-594.
  5. Zouboulis CC, Further Evidence of Sebaceous Differentiation Uniqueness: Holocrine Secretion of Sebocytes Is a Multistep, Cell-Specific Lysosomal DNase2-Mediated Mode of Programmed Cell Death. Journal of Investigative Dermatology 2017;137:537-539.
  6. Xie HT, Sullivan DA, Chen D, et al., Biomarkers for Progenitor and Differentiated Epithelial Cells in the Human Meibomian Gland. STEM CELLS Translational Medicine 2018;7:887-892.
  7. Liu S, Hatton MP, Khandelwal P, et al., Culture, immortalization, and characterization of human meibomian gland epithelial cells. Investigative Ophthalmology & Visual Science 2010;51:3993-4005.