Summary: The CellExIt#1 symposium gathered for the first time investigators working on cell extrusion. This report offers a panoramic view of the research teams and ongoing projects of the field.

A project page on therapy-associated immune remodeling in vitiligo skin using spatial transcriptomic analysis.

A project page on extracellular signaling, integrin trafficking, and transcriptional control of keratinocyte stemness.

Background Keratinocyte stem cells are essential for maintaining epidermal homeostasis and enabling efficient tissue repair. Regulation of their self-renewal and differentiation is critical, as its disruption can impair regeneration and drive pathological conditions such as chronic wounds and cancer. We previously identified the matricellular protein Mindin as a key regulator of keratinocyte stemness through its interaction with the αMβ2 (CD11b/CD18) integrin and subsequent activation of the transcription factor STAT3. However, the mechanism connecting Mindin and integrin at the cell surface to the intracellular activation of STAT3 remained undefined. Methods We employ biochemical and imaging analysis along with molecular dynamics simulations to dissect Mindin–integrin–STAT3 signalling in primary mouse keratinocytes. Stemness of epidermal keratinocytes are assessed using bulk RNA sequencing, quantitative PCR, and cell-based assays. Results Our work demonstrates that the F-Spondin domain of Mindin constitutes the minimal integrin-binding module required to initiate downstream signalling. F-Spondin binding to the integrin at the plasma membrane does not elicit the full activation state of the integrin. Instead, it promotes Src-kinase dependent endocytosis of the integrin receptor to the early endosomes. Analysis of integrin conformational dynamics reveals that the acidic environment of early endosomes is essential to achieve a signalling-competent state. This mechanism extends to pathological contexts, as we demonstrate a requirement for endocytosis in activating STAT3 signalling and preserving stem-like properties in a cancer stem cell model. Conclusions These findings highlight a previously unrecognized layer of spatial control in integrin signalling, confirming endosomal trafficking as a critical determinant of stem cell behaviour and offering new conceptual and therapeutic opportunities across regenerative biology and cancer.

Narrow-band UVB (NBUVB) phototherapy is an effective, non-invasive treatment for vitiligo vulgaris, but its impact on dermal T cells—the key drivers of disease—remains unclear. Using spatial transcri...

Happy to collaborate with my colleague Abhik Dutta on this fantastic work. This project pushed me to think about disease and treatment at the level of tissue architecture. Vitiligo is clearly shaped ...

PhD candidate researching mechanobiology and epigenetic regulation in skin biology at inStem, India.

Fibrosis results from excessive extracellular matrix (ECM) deposition, which causes tissue stiffening and organ dysfunction. Activated fibroblasts, central to fibrosis, exhibit increased migration, proliferation, contraction, and ECM production. However, it remains unclear if the same fibroblast performs all of the processes that fall under the umbrella term of “activation.” Owing to fibroblast heterogeneity in connective tissues, subpopulations with specific functions may operate under distinct regulatory controls. Using a transgenic mouse model of skin fibrosis, we found that Mindin (also known as spondin-2), secreted by Snail-transgenic keratinocytes, differentially regulates fibroblast subpopulations. Mindin promotes migration and inflammatory gene expression in SCA1+ dermal fibroblasts via Fyn kinase. In contrast, it enhances contractility and collagen production in papillary CD26+ fibroblasts through c-Src signaling. Moreover, in the context of the fibrotic microenvironment of the tumor stroma, we found that differential responses of resident fibroblast subpopulations to Mindin extend to the generation of functionally heterogeneous cancer-associated fibroblasts. This study identifies Mindin as a key orchestrator of dermal fibroblast heterogeneity, reshaping cellular dynamics and signaling diversity in the complex landscapes of skin fibrosis and cancer.