Transit-Amplifying Cells in the Fast Lane from Stem Cells towards Differentiation

Abstract

Stem cells have a high potential to impact regenerative medicine. However, stem cells in adult tissues often proliferate at very slow rates. During development, stem cells may change first to a pluripotent and highly proliferative state, known as transit-amplifying cells. Recent advances in the identification and isolation of these undifferentiated and fast-dividing cells could bring new alternatives for cell-based transplants. The skin epidermis has been the target of necessary research about transit-amplifying cells; this work has mainly been performed in mammalian cells, but further work is being pursued in other vertebrate models, such as zebrafish. In this review, we present some insights about the molecular repertoire regulating the transition from stem cells to transit-amplifying cells or playing a role in the transitioning to fully differentiated cells, including gene expression profiles, cell cycle regulation, and cellular asymmetrical events. We also discuss the potential use of this knowledge in effective progenitor cell-based transplants in the treatment of skin injuries and chronic disease.

Conditional ablation of p130Cas/BCAR1 adaptor protein impairs epidermal homeostasis by altering cell adhesion and differentiation

“…Since epidermal stratification involves delamination and asymmetrical cell division of basal cells [ 7 , 8 ], and we observed a higher percentage of K14 positive cells in the suprabasal layers of the p130CasKO, we hypothesized that p130Cas deletion might impact progenitor cells commitment toward differentiation. Consistently, we found that freshly isolated p130CasKO primary keratinocytes have an overall reduced clonogenic capacity with a strong reduction of colonies displaying holoclone- and meroclone-like morphology, which was also maintained in second-generation clonogenic assays (Fig.…”

“…In the epidermis, the stem cell compartment undergoes asymmetrical cell division generating committed, differentiating progenitor cells that are further subjected to few rounds of cell division after which they undergo terminal differentiation by moving upward [ 8 , 30 ]. The prerequisite to generate these progenitor cells is loss of integrin-based adhesion.…”

“…The first one involving the basal cells detachment and transition from the basement membrane to the suprabasal layers. The second mechanism accounts for the asymmetrical cell division of stem cells residing in the basal layer that generate a suprabasal cell that is committed to terminal differentiation but still undergoes a limited number of cell division and a slow cycling cell that remains confined into the basal layers [ 6 – 8 ].…”

Recent Advances in the Genetic, Anatomical, and Environmental Regulation of the C. elegans Germ Line Progenitor Zone

“…The existence of a transit amplifying (TA) population in the germ line has been contentious. TA cells are stem cell progeny that have left the niche but have not yet differentiated and instead continue to undergo some number of mitotic divisions before differentiating [ 106 , 107 ]. Experiments using emb-30 mutants blocked for the metaphase-to-anaphase transition at the restrictive temperature show that a distal 6–8 rows of germ cells arrest in metaphase and fail to acquire markers of differentiation as rapidly as more proximal germ cells in the PZ [ 95 ]; the more proximal cells also rapidly enter meiosis upon refeeding after starvation [ 105 ].…”

Oxygen battle in the gut: Hypoxia and hypoxia-inducible factors in metabolic and inflammatory responses in the intestine

“…Moreover, in tissues the cellular metabolic pathways utilized for growth and function largely depend on the proliferative nature of the cell type. As mentioned above, the colon and small intestine contain both highly proliferative stem cells and transit-amplifying progenitor population and post-mitotic differentiated cells (48). The post-mitotic differentiated cells have a high rate of energy expenditure due to energy-consuming digestive, secretory, and absorptive processes (49).…”