Distinct contribution of stem and progenitor cells to epidermal maintenance

Abstract

The skin interfollicular epidermis (IFE) is the first barrier against the external environment and its maintenance is critical for survival. Two seemingly opposite theories have been proposed to explain IFE homeostasis. One posits that IFE is maintained by long-lived slow-cycling stem cells that give rise to transit-amplifying cell progeny, whereas the other suggests that homeostasis is achieved by a single committed progenitor population that balances stochastic fate. Here we probe the cellular heterogeneity within the IFE using two different inducible Cre recombinase–oestrogen receptor constructs targeting IFE progenitors in mice. Quantitative analysis of clonal fate data and proliferation dynamics demonstrate the existence of two distinct proliferative cell compartments arranged in a hierarchy involving slow-cycling stem cells and committed progenitor cells. After wounding, only stem cells contribute substantially to the repair and long-term regeneration of the tissue, whereas committed progenitor cells make a limited contribution.

Identification of Lineage-Uncommitted, Long-Lived, Label-Retaining Cells in Healthy Human Esophagus and Stomach, and in Metaplastic Esophagus

“…Furthermore and to substantiate this later point a recent publication has shown that in skin the epidermis slowly cycling cells exist and can repopulate the entire damaged tissue 13 . These experiments support the position of esophageal squamous cell LRCs identified in a murine model and take it further into man in health and disease 43 .…”

“…1,[12][13] Analysis for human LGR5 mRNA showed that expression was indeed located at the base of the Barrett's glands ( Figure 5E (light field) (dark field) F)). However no expression was seen in the normal squamous esophagus or in the submucosal glands/ducts.…”

“…These confusing data are particularly troublesome in the case of the esophagus and the common premalignant lesion Barrett's Esophagus (BE). First there have been reports of fast cycling cells with stem cell capacity in animal models and some of them indicate a residual stem cell population is needed while others do not [11][12][13][14][15] . Second some additional reports have implicated endodermal (including epithelial) embryonic markers in man but their relevance to human stem cells remains unclear 16 .…”

“…Despite these problems other techniques which trace lineage by genetic analyses strongly favour the likelihood of common stem cells between squamous and columnar esophageal mucosa [19][20][21][22][23][24] . The site of stem cells in BE has been more problematic [10][11][12][13][14][15] as well as the availability of true 'biomarkers' of stem cells [16][17][18] .…”

Hasard et destinée cellulaire

“…Il a été observé chez E. coli [14,15] et Lactococcus lactis [16] qu'une fraction des cellules était capable (Figure 3). Une étude similaire de l'épiderme de souris montre une dynamique plus hiérarchique, entre un type prolifératif et un type différencié, mais toujours suivant des règles de transitions aléatoires [26]. Ainsi, si les processus de transitions aléatoires semblent être répandus (également observés pour les cellules souches pluripotentes [27] et les cellules immunitaires [28]), les architectures génétiques sous-jacentes semblent très diverses.…”