Altered ubiquitin signaling induces Alzheimer's disease-like hallmarks in a three-dimensional human neural cell culture model.

Alzheimer's disease (AD) is characterized by toxic protein accumulation in the brain. Ubiquitination is essential for protein clearance in cells, making altered ubiquitin signaling crucial in AD development. A defective variant, ubiquitin B + 1 (UBB), created by a non-hereditary RNA frameshift mutation, is found in all AD patient brains post-mortem.

Thy1 marks a distinct population of slow-cycling stem cells in the mouse epidermis.

The presence of distinct stem cells that maintain the interfollicular epidermis is highly debated. Here, we report a population of keratinocytes, marked by Thy1, in the basal layer of the interfollicular epidermis. We find that epidermal cells expressing differential levels of Thy1 display distinct transcriptional signatures.

THY1-mediated mechanisms converge to drive YAP activation in skin homeostasis and repair.

Anchored cells of the basal epidermis constantly undergo proliferation in an overcrowded environment. An important regulator of epidermal proliferation is YAP, which can be controlled by both cell-matrix and cell-cell interactions. Here, we report that THY1, a GPI-anchored protein, inhibits epidermal YAP activity through converging molecular mechanisms.

Fetomaternal microchimerism in tissue repair and tumor development.

In various placental mammals, the bidirectional exchange of cells during pregnancy can lead to the acquisition of genetically unique cells that can persist in both mother and child for decades. Over the years, it has become increasingly clear that this phenomenon, termed fetomaternal microchimerism may play key roles in a number of biological processes. In this perspective, we explore the concept of fetomaternal microchimerism and outline how fetal microchimeric cells are detected and immunologically tolerated within the maternal setting.

Apoptotic cells represent a dynamic stem cell niche governing proliferation and tissue regeneration.

Stem cells (SCs) play a key role in homeostasis and repair. While many studies have focused on SC self-renewal and differentiation, little is known regarding the molecular mechanism regulating SC elimination and compensation upon loss. Here, we report that Caspase-9 deletion in hair follicle SCs (HFSCs) attenuates the apoptotic cascade, resulting in significant temporal delays.

YAP and β-Catenin Cooperate to Drive Oncogenesis in Basal Breast Cancer.

Targeting cancer stem cells (CSC) can serve as an effective approach toward limiting resistance to therapies. While basal-like (triple-negative) breast cancers encompass cells with CSC features, rational therapies remain poorly established. We show here that the receptor tyrosine kinase Met promotes YAP activity in basal-like breast cancer and find enhanced YAP activity within the CSC population.

Blimp1 cells generate functional mouse sebaceous gland organoids in vitro.

Most studies on the skin focus primarily on the hair follicle and interfollicular epidermis, whereas little is known regarding the homeostasis of the sebaceous gland (SG). The SG has been proposed to be replenished by different pools of hair follicle stem cells and cells that resides in the SG base, marked by Blimp1. Here, we demonstrate that single Blimp1 cells isolated from mice have the potential to generate SG organoids in vitro.

The ARTS of Cell Death.

Although much is known regarding intestinal stem cell (ISC) self-renewal and differentiation, the specific mechanisms used for their elimination is unclear. We recently discovered that the pro-apoptotic protein ARTS, a isoform, interacts with X-linked inhibitor of apoptosis (XIAP) in the ISC niche to regulate stem cell survival during intestinal homeostasis and regeneration. These findings point to an intriguing avenue of translational research, examining how manipulation of stem cell apoptosis through the ARTS/XIAP module can affect stem-cell-dependent processes.

ARTS mediates apoptosis and regeneration of the intestinal stem cell niche.

Stem cells (SCs) play a pivotal role in fueling homeostasis and regeneration. While much focus has been given to self-renewal and differentiation pathways regulating SC fate, little is known regarding the specific mechanisms utilized for their elimination. Here, we report that the pro-apoptotic protein ARTS (a Septin4 isoform) is highly expressed in cells comprising the intestinal SC niche and that its deletion protects Lgr5 and Paneth cells from undergoing apoptotic cell death.

Caspase-3 Regulates YAP-Dependent Cell Proliferation and Organ Size.

Apoptosis culminates in the activation of caspase-3, which plays an important role in implementing the cell death program. Here, we reveal a non-apoptotic role of caspase-3 as a key regulator of cell proliferation and organ size. Caspase-3 is specifically activated in the proliferating cells of the sebaceous gland, but does not instruct cell elimination.

The bad seed: Cancer stem cells in tumor development and resistance.

Over the past two decades cancer stem cells (CSCs) have emerged as essential players in the pathogenesis of cancer, with the capacity to initiate, maintain and repopulate different tumors. Within the tumor bulk, CSCs represent a small subpopulation, bestowed with the capacity to self-renew and yield heterogeneous lineages of cancer cells. In many scenarios, CSCs exhibit increased resistance toward irradiation and chemotherapy, and given their spectacular ability to replenish the tumor, they constitute a substantial therapeutic challenge.