Airway Hillocks: Injury-Resistant Reservoirs of Unique Plastic Stem Cells with Implications for Airway Regeneration and Squamous Metaplasia

Alapfogalmak

Airway hillocks are stratified epithelial structures containing a unique population of basal stem cells that can continually replenish the overlying squamous barrier cells and resist a broad spectrum of injuries, playing a key role in airway regeneration and the development of squamous metaplasia.

Kivonat

The content describes the discovery and characteristics of airway hillocks, which are stratified epithelial structures in the airway with a unique population of basal stem cells. These hillock basal stem cells exhibit higher turnover and regenerative capacity compared to the abundant, largely quiescent classic pseudostratified airway epithelium.

Key insights:

• Hillock basal stem cells express genes associated with barrier function and cell adhesion, and can continually replenish the overlying squamous barrier cells.
• Hillocks are remarkably resistant to a broad range of injuries, including toxins, infection, acid, and physical damage, because the overlying squamous cells shield the underlying basal stem cells.
• Hillock basal stem cells are capable of massive clonal expansion, which is sufficient to resurface denuded airway and eventually regenerate the normal airway epithelium with all its component cell types.
• Hillock basal stem cells preferentially stratify and keratinize in the setting of retinoic acid signaling inhibition, a known cause of squamous metaplasia.
• The authors show that mouse hillock expansion is the cause of vitamin A deficiency-induced squamous metaplasia.
• The authors also identify human hillocks whose basal stem cells can generate functional squamous barrier structures in culture.
• The discovery of hillocks reframes the understanding of airway epithelial regeneration and suggests that hillocks are one origin of 'squamous metaplasia', which is considered a precursor of lung cancer.

Statisztikák

Hillocks persist for months and have a unique population of basal stem cells.
Hillock basal stem cells exhibit dramatically higher turnover than the abundant, largely quiescent classic pseudostratified airway epithelium.
Hillock basal stem cells are capable of massive clonal expansion that is sufficient to resurface denuded airway and regenerate normal airway epithelium.

Idézetek

"Hillock basal stem cells preferentially stratify and keratinize in the setting of retinoic acid signalling inhibition, a known cause of squamous metaplasia."
"The existence of hillocks reframes our understanding of airway epithelial regeneration."
"We show that hillocks are one origin of 'squamous metaplasia', which is long thought to be a precursor of lung cancer."

Főbb Kivonatok

Airway hillocks are injury-resistant reservoirs of unique plastic stem cells - Nature

by Brian Lin,Vi... : www.nature.com 05-01-2024

https://www.nature.com/articles/s41586-024-07377-1

Mélyebb kérdések

What are the specific molecular mechanisms that enable hillock basal stem cells to resist a broad spectrum of injuries?

Hillock basal stem cells possess unique molecular mechanisms that contribute to their remarkable injury resistance. One key factor is the expression of genes associated with barrier function and cell adhesion, which help in maintaining the integrity of the squamous barrier cells that shield these stem cells from various injuries. Additionally, the high turnover rate of hillock basal stem cells allows for rapid replenishment of damaged cells, ensuring the continuous regeneration of the airway epithelium. These stem cells also exhibit the capability of massive clonal expansion, enabling them to resurface denuded areas of the airway efficiently. Overall, the combination of gene expression profiles, rapid turnover, and clonal expansion capacity contributes to the injury-resistant nature of hillock basal stem cells.

How do the regenerative capabilities of hillock basal stem cells compare to those of other known airway epithelial stem cell populations?

The regenerative capabilities of hillock basal stem cells set them apart from other known airway epithelial stem cell populations. Unlike the largely quiescent classic pseudostratified airway epithelium, hillock basal stem cells exhibit significantly higher turnover rates, allowing for rapid cell replenishment and regeneration of the airway epithelium. Moreover, hillock basal stem cells have the unique ability to undergo massive clonal expansion, which is essential for resurfacing denuded areas of the airway and regenerating all six component cell types of the normal airway epithelium. This regenerative capacity surpasses that of other airway epithelial stem cell populations, making hillock basal stem cells a crucial player in airway epithelial regeneration.

Given the link between squamous metaplasia and lung cancer, what are the potential implications of the discovery of hillocks for understanding and treating lung cancer?

The discovery of hillocks and their association with squamous metaplasia has significant implications for understanding and potentially treating lung cancer. Squamous metaplasia, traditionally considered a precursor of lung cancer, is now linked to the expansion of hillock basal stem cells in response to vitamin A deficiency. This finding suggests that hillocks may serve as one origin of squamous metaplasia, shedding light on the mechanisms underlying the progression from metaplasia to lung cancer. By understanding the role of hillocks in squamous metaplasia, researchers may uncover new targets for intervention and treatment strategies aimed at preventing the development of lung cancer. Additionally, the identification of human hillocks capable of generating functional squamous barrier structures in culture opens up possibilities for studying lung cancer pathogenesis and developing novel therapeutic approaches targeting these unique stem cell populations.