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Updated: Nov 18, 2025
Stepwise Cell Seeding on Tessellated Scaffolds to Study Sprouting Blood Vessels
Published on: January 14, 2021
Ryo Ichijo1, Mio Kabata2, Hiroyasu Kidoya3
1Department of Biosystems Science, Institute for Frontier Life and Medical Science, Kyoto University, Sakyo-ku, Kyoto 606-8507, Japan.
This study explores how stem cells regulate tissue scaling in dynamic organs like the skin. The researchers found that interfollicular epidermal stem cells (IFESCs) form clusters of proliferating cells in expanding skin regions. These clusters are shaped by Tbx3+ basal cells, which are supported by vasculature and Adam8 signaling. The study shows that Tbx3+ basal cells differentiate during pregnancy and remain as long-term stem cells in plantar skin. Mechanical stretch is proposed as an external cue for these processes. The findings suggest that vasculature-driven stem cell activity explains how skin adjusts its size during physiological changes. This work provides new insights into tissue scaling in dynamic organs.
Area of Science:
Background:
Tissue homeostasis depends on stem cell regulation, but the mechanisms governing tissue scaling in dynamic organs remain unclear. Prior research has shown that stem cells manage proliferation and differentiation to maintain tissue integrity. However, how these processes coordinate organ size adjustments is less understood. No prior work had resolved the role of vasculature in dynamic skin growth. This gap motivated investigations into how stem cells interact with their environment during tissue expansion. The epidermis, particularly in regions like the abdomen and soles, offers a model for studying these processes. Established knowledge includes the role of interfollicular epidermal stem cells in skin maintenance. Yet, the specific signaling and structural cues enabling tissue scaling remained unexplored. This paper contributes by identifying vasculature-driven mechanisms in epidermal scaling.
Purpose Of The Study:
This study aimed to uncover how stem cells regulate tissue scaling in dynamic organs like the skin. Specifically, the researchers focused on how interfollicular epidermal stem cells (IFESCs) function during tissue expansion. They sought to determine the role of vasculature in coordinating epidermal growth. The study also aimed to identify external cues influencing stem cell behavior in dynamic skin regions. By examining pregnant mice and plantar epidermis, the researchers tested how IFESCs respond to mechanical and developmental signals. The goal was to establish whether Tbx3+ basal cells serve as long-term stem cells in these contexts. The study aimed to clarify the relationship between vasculature and stem cell activity in tissue scaling. These findings could help explain how skin adjusts its size during physiological changes.
Main Methods:
The researchers used clonal lineage tracing to track the behavior of interfollicular epidermal stem cells (IFESCs) in expanding skin regions. They analyzed the abdominal epidermis of pregnant mice and the plantar epidermis to observe stem cell dynamics. Tbx3+ basal cells were identified using fluorescent markers and molecular profiling. Adam8-extracellular signal-regulated kinase signaling was assessed to determine its role in epidermal cluster formation. The team examined how Tbx3+ basal cells differentiate during pregnancy and post-parturition. They also assessed the stability of Tbx3+ basal cells in plantar skin over time. Mechanical stretch was tested as an external cue influencing vasculature-driven stem cell activity. The study combined histological analysis with functional assays to validate vasculature dependency in stem cell regulation.
Main Results:
The study found that interfollicular epidermal stem cells (IFESCs) form basal epidermal proliferating clusters (EPCs) in expanding abdominal skin. Tbx3+ basal cells were shown to be central to EPC formation and differentiation. Adam8-extracellular signal-regulated kinase signaling was activated in neighboring cells of Tbx3+ basal cells. Clonal lineage tracing revealed that Tbx3+ basal cell clones emerge during pregnancy and differentiate after parturition. In plantar epidermis, Tbx3+ basal cells remained as long-lived stem cells to sustain EPCs. Vasculature was identified as a key dependency for Tbx3+ basal cell function. Mechanical stretch was confirmed as an external cue for EPC formation. These findings suggest that vasculature-driven stem cell activity explains tissue scaling in dynamic skin regions.
Conclusions:
The authors propose that vasculature-driven interfollicular epidermal stem cells (IFESCs) regulate tissue scaling in dynamic skin regions. Their findings suggest that Tbx3+ basal cells are central to forming and maintaining epidermal proliferating clusters (EPCs). The study shows that Adam8-extracellular signal-regulated kinase signaling is activated in neighboring cells of Tbx3+ basal cells. Vasculature is identified as a key dependency for IFESC function in tissue scaling. Mechanical stretch is proposed as an external cue for EPC formation. The results suggest that Tbx3+ basal cells differentiate during pregnancy and remain as long-lived stem cells in plantar skin. The authors conclude that vasculature-mediated IFESC regulation explains how epidermis adjusts with dermal constituents. These findings provide a framework for understanding tissue scaling in dynamic organs.
The authors propose that vasculature-driven interfollicular epidermal stem cells (IFESCs) regulate tissue scaling through Tbx3+ basal cells and Adam8-extracellular signal-regulated kinase signaling.
Tbx3+ basal cells form epidermal proliferating clusters (EPCs) and differentiate during pregnancy, while remaining as long-lived stem cells in plantar skin.
Vasculature is identified as a key dependency for Tbx3+ basal cell activity and EPC formation in dynamic skin regions.
This signaling is activated in neighboring cells of Tbx3+ basal cells, suggesting a role in coordinating epidermal cluster formation.
The authors propose that mechanical stretch acts as an external cue for vasculature-driven EPC formation in expanding skin regions.
The authors suggest that vasculature-mediated IFESC regulation explains how the epidermis adjusts its size in coordination with dermal constituents.
