In this issue, Almasoud et al. (https://doi.org/10.1083/jcb.202504139) report a surprising finding that epithelial cell polarity is present in a tissue with no known polarized function, in a cell type that was assumed to show a distinct lack of such polarity-the mesenchymal cells of the Drosophila fat body. Exceptions such as this help to broaden our understanding of the use of regulators and pathways we thought we fully understood.

Enamel, the hardest mineralized material in the human body, protects the underlying living tissues, the dentin and pulp of the tooth. However, over 90% of adults have lost or damaged enamel and cannot regenerate the protective structure due to lack of enamel-producing cells, ameloblasts. iPSC-derived secretory Ameloblasts (isAM) have promise in future regenerative dentistry. Today, it is not known why iAM maturation requires intimate contact with the dentin-producing cell type, odontoblast. Here, we reveal that one of the critical signaling ligands emanating from odontoblasts for ameloblast maturation is Delta, the ligand for Notch receptor. We showed that our designed, soluble Notch agonist can induce iAM organoid maturation in an unprecedented manner, without interactions with odontoblast layer. Notably, soluble Notch agonist induces the iAM maturation to a novel, WDR72-positive mature secretory AM stage (ismAM) in our ameloblast organoid model. When transplanted under the kidney capsule of NOD-SCID mice, these ismAM organoids generated enamel-like calcified material, as confirmed by microCT analysis, marking the first demonstration that Notch-activated iAM organoids can form such tissue in vivo. This novel maturation procedure enabled us to analyze the specific requirements of DLX3 function in ameloblasts, independent of its known function in odontoblasts. We now show that DLX3, a gene associated with Amelogenesis Imperfecta, is required on a cell-autonomous manner in human ameloblasts for the expression of Enamelin, MMP20, and WDR72, a role not previously demonstrated in mouse models.

Spatial transcriptomics in the human left atrial appendage and pulmonary vein sleeve.

Live cell imaging of exogenous α-synuclein fibrils in primary microglia and neuron co-cultures.

The role of AP-1 in distinct cardiac cell types: Pathological repair and maladaptive remodeling.

Cellular insights into hydrocephalus: The diverse roles and intricate crosstalk of multiple cell types.

WATER roles in cells: Biological and biophysical perspectives.

Matrix-bound nanovesicles drive the engineering of immunomodulatory meshes for abdominal hernia repair.

Oriented porous microtubules combined with CNTF-delivery directional guide axonal regeneration after traumatic optic neuropathy.

Recent fossil discoveries and advances in plant phylogeny have renewed debate about the most recent common ancestor (MRCA) of land plants and the evolution of its fundamental organs and tissues. We re-investigate the vascular system of Horneophyton lignieri, an exceptionally preserved Rhynie Chert fossil central to understanding early plant evolution. Using confocal laser scanning microscopy combined with 3D modelling, we achieved higher resolution and precision in reconstructing cell morphology than earlier studies that relied on white light microscopy. We show that the vascular system of H. lignieri lacks distinct xylem and phloem tissues, contrary to prior assumptions. Instead, tissues with transfer cell-like structures are prominent, and both cell type and cell wall development vary with position in the plant. These findings indicate that the ancestral vascular system of land plants likely consisted of a single type of conducting cell capable of both solute transport and water conduction. Our results show that H. lignieri is not a tracheophyte, supporting emerging models of a morphologically and cellularly complex MRCA for land plants.

Specific generation of reactive oxygen species (ROS) is important for signalling and defence in many organisms. In plants, different types of ROS serve useful biological functions in the extracellular space (apoplast), influencing polymer structures as well as signalling during immune responses. The current knowledge of apoplastic ROS dynamics is limited, as dynamic monitoring of extracellular redox processes in vivo remains difficult. We employed evolutionary distant land plant model species from bryophytes and flowering plants to test whether the genetically encoded redox biosensor roGFP2-Orp1 can be used to assess extracellular redox dynamics. Secreted roGFP2-Orp1 can provide information about local diffusion barriers and protein cysteinyl oxidation rate in the apoplast, after pre-reduction. Observed re-oxidation rates were slow - within the range of hours. Compared to Physcomitrium patens, re-oxidation in Arabidopsis thaliana was faster and increased after triggering an immune response. Comparing roGFP2-Orp1 signals in tip-growing P. patens protonema and Nicotiana tabacum pollen tubes, we consistently find no intracellular redox gradient, but a partially reduced extracellular sensor in pollen tubes. Our data indicate differences in extracellular oxidative processes between species and within a species, depending on cell type and immune signalling.

A functionally relevant model for interrogating brain tumor-endothelial cell interactions.

Causal evidence linking chronic pain genetics to late-onset asthma via the nervous system.

Quantitative trait loci as indicators of potential susceptibility to allele-specific dropout for forensic RNA markers.

Exosomal MicroRNAs: From cellular communication to disease biomarkers.

Kidney fibrosis is characterized by excessive deposition of extracellular matrix, which is ultimately disrupting normal renal architecture. Despite its clinical relevance, no targeted antifibrotic therapies are currently available. Myofibroblasts, primarily derived from pericytes and resident fibroblasts, are key effectors of fibrosis due to their high extracellular matrix production. Here, we tested the hypothesis that ferroptosis induction would enable the targeted elimination of activated kidney fibroblasts. We found that kidney fibroblasts exhibit marked sensitivity to ferroptotic cell death upon exposure to the ferroptosis inducer RAS-selective lethal 3 (RSL3), an effect further amplified by transforming growth factor-β stimulation. In tissue slice cultures of murine fibrotic kidneys, RSL3 eliminated myofibroblasts without causing overt damage to other cell types. Extending these findings in vivo, we applied a postischemia/reperfusion model of kidney fibrosis and demonstrated that repeated low-dose systemic administration of RSL3 significantly reduced the activated fibroblast population without inducing appreciable injury to parenchymal cells. These results provide proof-of-principle that the ferroptosis susceptibility of activated fibroblasts may offer a potential strategy for the selective depletion of profibrotic effector cells in kidney fibrosis.NEW & NOTEWORTHY This study reveals ferroptosis, a pharmacologically inducible form of cell death, as a novel mechanism to eliminate activated fibroblasts, the main drivers of kidney fibrosis. Due to their high ferroptosis sensitivity, these cells are selectively depleted by RSL3 in vitro, in kidney tissue slice cultures, and in fibrotic kidneys in vivo. These findings highlight ferroptosis induction as a promising antifibrotic strategy in kidney disease.

CD36 may regulate glycolytic and steroidogenic processes but not the fatty acid uptake in bovine granulosa cells.

Influence of storage conditions on viability of hematopoietic stem cells and leukocyte subpopulations in fresh and cryopreserved umbilical cord blood samples.

Non-neuronal cell microenvironment control retinal vascular remodeling by CST3 in the oxygen-induced retinopathy in mice.

Intrinsically disordered proteins and liquid-liquid phase separation in drug discovery.