KRT6A and KRT17 Mark Distinct Stem Cell Populations in the Adult Palpebral Conjunctiva and Meibomian Gland
Year: 2025
Type: article
Abstract: Purpose To investigate whether KRT6A or KRT17 label self-renewing stem cells (SCs) in adult Meibomian gland (MG) and palpebral conjunctiva (PC) homeostasis and explore the mechanisms that regulate their expression in these tissues. Methods KRT6A and KRT17 expression in adult mouse MG and PC was examined by single nucleus RNA sequencing and immunofluorescence (IF). Bromodeoxyuridine pulse-chase assays were conducted to assess the turnover rate of PC progenitor cells. Lineage tracing experiments were performed using Krt6a-Cre ERT2 and Krt17-Cre ERT2 mice carrying Rosa26R nTnG or Rosa26R mTmG reporter. As Hedgehog (Hh) signaling, the histone deacetylase HDAC3, and the transcription factor KLF4, regulate KRT6A and KRT17 in other contexts, IF was conducted to assess the in vivo effects of overexpression of the Hh pathway activator GLI2ΔN, and inducible epithelial deletion of Hdac3 or Klf4 , on KRT6A and KRT17 expression in the MG and PC. Results KRT6A and KRT17 are primarily expressed in the MG central duct and ductules. KRT6A also shows robust expression in PC. MG and PC epithelial progenitor cells turn over within 14 days. Lineage tracing indicated that Krt17 labels self-renewing SCs in the MG whereas Krt6a labels SCs in the PC. GLI2ΔN overexpression induced ectopic KRT17 expression in MG acini and PC but did not affect KRT6A expression in either MG or PC. Hdac3 deficiency caused expanded expression of KRT6A and KRT17 in MG acini and ectopic KRT17 expression in PC. Klf4 deletion resulted in ectopic KRT17 expression in PC but did not influence KRT6A expression in MG or PC. Conclusions Krt6a - and Krt17 -expressing cells contribute to adult PC and MG homeostasis, respectively. KRT17 expression is enhanced by GLI2ΔN, and suppressed by HDAC3 and KLF4, whereas KRT6A expression is controlled only by HDAC3.
Source: Cells
Authors: Xuming Zhu, Mingang Xu, David M. Owens, Sarah E. Millar
Institutions: Icahn School of Medicine at Mount Sinai, Columbia University
Language: English
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,258
Awards: G1030364335, KLF-mediated coordination of signaling and epigenetic mechanisms in the skin, G5820008682, G7168188781, G7318480064, Molecular mechanisms controlling skin heterogeneity, Investigating the role for Utrophin in age-related decline of the Merkel lineage, Skin Biology and Diseases Resource-based Center at Mount Sinai
OpenAlex ID: W7114893595