Development

Skeletal muscle experiences a decline in lean mass and regenerative potential with age, in part due to intrinsic changes in progenitor cells. However, it remains unclear how age-related changes in progenitors manifest across a differentiation trajectory. Here, we perform single-cell RNA sequencing (RNA-seq) on muscle mononuclear cells from young and aged mice and profile muscle stem cells (MuSCs) and fibro-adipose progenitors (FAPs) after differentiation.

Background & Aims The homeostasis of the gastrointestinal epithelium relies on cell regeneration and differentiation into distinct lineages organised inside glands and crypts. Regeneration depends on WNT/β-Catenin pathway activation, but to understand homeostasis and its dysregulation in disease we need to identify the signalling microenvironment governing cell differentiation. By using gastric glands as a model, we have identified the signals inducing differentiation of surface mucus-, zymogen- and gastric acid- producing cells.

Fibroblast-like synoviocytes (FLS) and articular chondrocytes (AC) derive from a common pool of embryonic precursor cells. They are currently believed to engage in largely distinct differentiation programs to build synovium and articular cartilage and maintain healthy tissues throughout life. We tested this hypothesis by deeply characterizing and comparing their transcriptomic attributes.

Members of the ADAMTS family have been implicated in various vascular diseases. However, their functional roles in early embryonic vascular development are unknown. In this study, we showed that Adamts18 is highly expressed at E11.5-E14.5 in cells surrounding the embryonic aortic arch (AOAR) and the common carotid artery (CCA) during branchial arch artery development in mice. Adamts18 deficiency was found to cause abnormal development of AOAR, CCA, and the 3rd and 4th branchial arch appendages, leading to hypoplastic carotid body, thymus, and variation of middle cerebral artery.

In mammalian ovaries, immature oocytes are reserved in primordial follicles until their activation for potential ovulation. Precise control of primordial follicle activation (PFA) is essential for reproduction, but how this is achieved is unclear. Here, we show that canonical wingless-type MMTV integration site family (WNT) signaling is pivotal for pre-granulosa cell (pre-GC) activation during PFA. We identified several WNT ligands expressed in pre-GCs that act in an autocrine manner.

Cystic fibrosis (CF) is a lethal autosomal recessive disorder that afflicts more than 70,000 people. People with CF experience multi-organ dysfunction resulting from aberrant electrolyte transport across polarized epithelia due to mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. CF-related lung disease is by far the most important determinant of morbidity and mortality.

Two inherent challenges in the mechanistic interpretation of protease-deficient phenotypes are defining the specific substrate cleavages whose reduction generates the phenotypes and determining whether the phenotypes result from loss of substrate function, substrate accumulation, or loss of a function(s) embodied in the substrate fragments. Hence, recapitulation of a protease-deficient phenotype by a cleavage-resistant substrate would stringently validate the importance of a proteolytic event and clarify the underlying mechanisms.

The lymphatic system is composed of a hierarchical network of fluid absorbing lymphatic capillaries and transporting collecting vessels. Despite distinct functions and morphologies, molecular mechanisms that regulate the identity of the different vessel types are poorly understood. Through transcriptional analysis of murine dermal lymphatic endothelial cells (LECs), we identified Foxp2, a member of the FOXP family of transcription factors implicated in speech development, as a collecting vessel signature gene.

Most nephrons are added in late gestation. Truncated extrauterine nephrogenesis in premature infants results in fewer nephrons and significantly increased risk for CKD in adulthood. To overcome the ethical and technical difficulties associated with studies of late-gestation human fetal kidney development, third-trimester rhesus macaques served as a model to understand lateral branch nephrogenesis (LBN) at the molecular level. Immunostaining and 3D rendering assessed morphology.

Cardiac cells generate and amplify force in the context of cardiac load, yet the membranous sheath enclosing the muscle fibers-the sarcolemma-does not experience displacement. That the sarcolemma sustains beat-to-beat pressure changes without experiencing significant distortion is a muscle-contraction paradox. Here, we report that an elastic element-the motor protein prestin (Slc26a5)-serves to amplify actin-myosin force generation in mouse and human cardiac myocytes, accounting partly for the nonlinear capacitance of cardiomyocytes.