Gastric epithelial stem cells in development, homeostasis and regeneration.

The stem/progenitor cell pool is indispensable for the development, homeostasis and regeneration of the gastric epithelium, owing to its defining ability to self-renew whilst supplying the various functional epithelial lineages needed to digest food efficiently. A detailed understanding of the intricacies and complexities surrounding the behaviours and roles of these stem cells offers insights, not only into the physiology of gastric epithelial development and maintenance, but also into the pathological consequences following aberrations in stem cell regulation. Here, we provide an insightful synthesis of the existing knowledge on gastric epithelial stem cell biology, including the in vitro and in vivo experimental techniques that have advanced such studies.

Unveiling the Influence of Tumor Microenvironment and Spatial Heterogeneity on Temozolomide Resistance in Glioblastoma Using an Advanced Human In Vitro Model of the Blood-Brain Barrier and Glioblastoma.

Glioblastoma (GBM) is the most common primary malignant brain cancer in adults with a dismal prognosis. Temozolomide (TMZ) is the first-in-line chemotherapeutic; however, resistance is frequent and multifactorial. While many molecular and genetic factors have been linked to TMZ resistance, the role of the solid tumor morphology and the tumor microenvironment, particularly the blood-brain barrier (BBB), is unknown.

Role of Wnt signaling in the maintenance and regeneration of the intestinal epithelium.

The intestinal epithelium plays a key role in digestion and protection against external pathogens. This tissue presents a high cellular turnover with the epithelium being completely renewed every 5days, driven by intestinal stem cells (ISCs) residing in the crypt bases. To sustain this dynamic renewal of the intestinal epithelium, the maintenance, proliferation, and differentiation of ISCs must be precisely controlled.

Targeted ablation of Lgr5-expressing intestinal stem cells in diphtheria toxin receptor-based mouse and organoid models.

Intestinal cells marked by Lgr5 function as tissue-resident stem cells that sustain the homeostatic replenishment of the epithelium. By incorporating a diphtheria toxin receptor (DTR) cassette linked to the Lgr5 coding region, native Lgr5-expressing cells are susceptible to ablation upon DT administration . A similar strategy can be used for Lgr5-expressing cells within organoids established from DTR models.

A monoastral mitotic spindle determines lineage fate and position in the mouse embryo.

During mammalian development, the first asymmetric cell divisions segregate cells into inner and outer positions of the embryo to establish the pluripotent and trophectoderm lineages. Typically, polarity components differentially regulate the mitotic spindle via astral microtubule arrays to trigger asymmetric division patterns. However, early mouse embryos lack centrosomes, the microtubule-organizing centres (MTOCs) that usually generate microtubule asters.

Cytoskeletal control of early mammalian development.

The cytoskeleton - comprising actin filaments, microtubules and intermediate filaments - serves instructive roles in regulating cell function and behaviour during development. However, a key challenge in cell and developmental biology is to dissect how these different structures function and interact in vivo to build complex tissues, with the ultimate aim to understand these processes in a mammalian organism. The preimplantation mouse embryo has emerged as a primary model system for tackling this challenge.

Keratins are asymmetrically inherited fate determinants in the mammalian embryo.

To implant in the uterus, the mammalian embryo first specifies two cell lineages: the pluripotent inner cell mass that forms the fetus, and the outer trophectoderm layer that forms the placenta. In many organisms, asymmetrically inherited fate determinants drive lineage specification, but this is not thought to be the case during early mammalian development. Here we show that intermediate filaments assembled by keratins function as asymmetrically inherited fate determinants in the mammalian embryo.

Expanding Actin Rings Zipper the Mouse Embryo for Blastocyst Formation.

Transformation from morula to blastocyst is a defining event of preimplantation embryo development. During this transition, the embryo must establish a paracellular permeability barrier to enable expansion of the blastocyst cavity. Here, using live imaging of mouse embryos, we reveal an actin-zippering mechanism driving this embryo sealing.