LGR5 is a conserved marker of hair follicle stem cells in multiple species and is present early and throughout follicle morphogenesis

Abstract

Hair follicle stem cells are key for driving growth and homeostasis of the hair follicle niche, have remarkable regenerative capacity throughout hair cycling, and display fate plasticity during cutaneous wound healing. Due to the need for a transgenic reporter, essentially all observations related to LGR5-expressing hair follicle stem cells have been generated using transgenic mice, which have significant differences in anatomy and physiology from the human. Using a transgenic pig model, a widely accepted model for human skin and human skin repair, we demonstrate that LGR5 is a marker of hair follicle stem cells across species in homeostasis and development. We also report the strong similarities and important differences in expression patterns, gene expression profiles, and developmental processes between species. This information is important for understanding the fundamental differences and similarities across species, and ultimately improving human hair follicle regeneration, cutaneous wound healing, and skin cancer treatment.

Novel porcine model reveals two distinct LGR5 cell types during lung development and homeostasis

“…To understand the spatial distribution of LGR5 expression throughout development and homeostasis, we used a transgenic porcine model expressing H2B-GFP under the control of the endogenous LGR5 promoter, generated as previously described (15). In cryosections imaged by confocal microscopy, co-staining fetal lungs with EpCAM for epithelial cells and vimentin for mesenchymal cells shows that in the fetal lung, two LGR5 + populations exist: one mesenchymal, surrounding all of the airways, and one epithelial, found in the bud tips (Figure 1A-C).…”

“…The disconnect between the human and murine cell population calls for an animal model that represents a more faithful anatomical and physiological model to the human lung (11)(12)(13)(14). Here we used a transgenic porcine model expressing a nuclear-localized histone H2B-GFP under the control of the endogenous LGR5 promoter (15) to study the role of LGR5 + cells in the lung. We show that in pigs, like humans, there are two roles for LGR5 + cells in homeostasis and development.…”

Ontogeny of cellular organization and LGR5 expression in porcine cochlea revealed using tissue clearing and 3D imaging

“…We recognized that the H2B-GFP turnover might affect some of the intensity qualifications but we believe the impact of turnover is minimal for three reasons: (1) A previous study shows that GFP protein expression correlates with LGR5 mRNA expression in the skin of the same pig model used in this study ( Polkoff et al., 2020 , 2022 ). (2) In the literature, the half-life for H2B-GFP is variable, and it depends on many factors such as cell turnover and activity, ranging from 4 to 8 h for dividing cells ( Liu et al., 2021 ; Xenopoulos et al., 2015 ) to 4–6 weeks into hematopoietic and epithelial stem cells ( Morcos et al., 2020 ; SanjeevWaghmare et al., 2008 ).…”

A LGR5 reporter pig model closely resembles human intestine for improved study of stem cells in disease

“…Healthy, crossbred LGR5‐H2B‐GFP littermate male and female pigs (10–40 weeks) were used for this study 40,41 . All LGR5‐H2B‐GFP animals were bred and raised in the animal facility of NCSU CVM.…”