Single-cell RNA sequencing identifies a migratory keratinocyte subpopulation expressing THBS1 in epidermal wound healing.

Keratinocyte differentiation is an intricate process that is regulated by multiple mediators. Using cultured human keratinocytes, we found that lysophosphatidic acid (LPA) induced the differentiation of a previously unsuspected keratinocyte subpopulation expressing the extracellular matrix protein, thrombospondin-1 (THBS1). This action of LPA was mediated by the RHO/ROCK-SRF signaling downstream of LPA and LPA receptors and required ERK activity.

Paradoxical activation of c-Src as a drug-resistant mechanism.

ATP-competitive inhibitors have been developed as promising anti-cancer agents. However, drug-resistance frequently occurs, and the underlying mechanisms are not fully understood. Here, we show that the activation of c-Src and its downstream phosphorylation cascade can be paradoxically induced by Src-targeted and RTK-targeted kinase inhibitors.

Multitarget super-resolution microscopy with high-density labeling by exchangeable probes.

We have developed a multitarget super-resolution microscopy technique called image reconstruction by integrating exchangeable single-molecule localization (IRIS). IRIS uses protein fragment-based probes that directly associate with and dissociate from their targets over durations on the order of tens of milliseconds. By integrating single-molecule localization and sequential labeling, IRIS enables unprecedented labeling density along multiple cellular structures.