Dynamic stem cell selection safeguards the genomic integrity of the epidermis.

Maintaining genomic integrity and stability is crucial for life; yet, no tissue-driven mechanism that robustly safeguards the epithelial genome has been discovered. Epidermal stem cells (EpiSCs) continuously replenish the stratified layers of keratinocytes that protect organisms against various environmental stresses. To study the dynamics of DNA-damaged cells in tissues, we devised an in vivo fate tracing system for EpiSCs with DNA double-strand breaks (DSBs) and demonstrated that those cells exit from their niches.

IGF-1R deficiency in human keratinocytes disrupts epidermal homeostasis and stem cell maintenance.

Background: Epidermal stem cells (ESCs) are keratinocytes that reside in the basal layer of the epidermis and mediate epidermal homeostasis. Insulin-like growth factor 1 (IGF-1) signaling through its receptor (IGF-1R) has been identified as an important regulator in rodent skin development and differentiation. However, the role of IGF-1/IGF-1R signaling in human keratinocytes is not yet well understood.

Type IV collagen aggregates promote keratinocyte proliferation and formation of epidermal layer in human skin equivalents.

Type IV collagen isolated from lens capsule without enzymatic treatment is known to form a gel under physiological condition and influences cellular activities. In case of human keratinocytes, the suppression of proliferation on reconstituted type IV collagen gels was reported in monolayer culture. In this study, we examined effects of type IV collagen isolated from porcine lens capsule on epidermal formation in human skin equivalents (HSEs).

Diminished WNT -> β-catenin -> c-MYC signaling is a barrier for malignant progression of BRAFV600E-induced lung tumors.

Oncogene-induced senescence (OIS) is proposed as a cellular defense mechanism that restrains malignant progression of oncogene-expressing, initiated tumor cells. Consistent with this, expression of BRAF(V600E) in the mouse lung epithelium elicits benign tumors that fail to progress to cancer due to an apparent senescence-like proliferative arrest. Here we demonstrate that nuclear β-catenin → c-MYC signaling is essential for early stage proliferation of BRAF(V600E)-induced lung tumors and is inactivated in the subsequent senescence-like state.

Role of the hypoxia response pathway in lens formation during embryonic development of Xenopus laevis.

The RING finger ubiquitin ligase seven in absentia homolog 2 (Siah2) was identified in the R7 photoreceptor cells of Drosophila melanogaster, and it regulates the stability of prolyl hydroxylase domains (PHDs), with a concomitant effect on HIF-1α availability in the hypoxia response pathway. We previously reported that the hypoxia response pathway contributes to eye development during the embryonic development of Xenopus laevis. In this paper, the role of Siah2-mediated hypoxia response pathway in eye development of X.