Apoptosis represents the dominant form of programmed cell death and plays critical roles in maintaining tissue and organ homeostasis. A notable population of extracellular vesicles (EVs) is generated during apoptosis, known as apoptotic vesicles (apoVs). These apoVs are increasingly the subject of studies concerning their identity and mechanisms of production, which have been revealed unique biological and functional characteristics that are emerging as crucial regulators for diverse processes. Furthermore, apoVs have been gradually noticed for their essential role in regulating the physiology of various organ systems in vivo, and growing evidence suggests that apoV dysregulation contributes to ageand pathology-associated tissue alterations. Importantly, apoVs can be therapeutically harnessed to unleash their potential in treating several diseases such as immune disorders, osteoporosis, cutaneous wound and acute liver failure; these vesicles, mainly derived from cultured mesenchymal stem cells, hold great translational promise. Here we review the current landscape of scientific knowledge about apoVs, with emphasis on mechanistic insights into how apoVs contribute to organismal health and disease, which also provide novel cell-free strategies for EV-based regenerative therapeutics.
Eukaryotic genomes are highly compacted in the cell nucleus. Two loci separated by a long linear distance can be brought into proximity in space through DNA-binding proteins and RNAs, which contributes profoundly to the regulation of gene expression. Recent technology advances have enabled the development and application of the chromosome conformation capture (3C) technique and a host of 3C-based methods that enable genome-scale investigations into changes in chromatin high-order structures during diverse physiological processes and diseases. In this review, we introduce 3C-based technologies and discuss how they can be utilized to glean insights into the impacts of three-dimensional (3D) genome organization in normal physiological and disease processes.
Adult neurogenesis declines with age due to the less functional neural stem cells (NSCs) and niches, but the underlying molecular bases for this impaired condition remain unclear. Here we analyzed >55,000 single-cell transcriptomes from two discrete neurogenic niches across the mouse lifespan, and identified new features and populations in NSCs, new markers, and neurogenic regional-specific alternations during aging. Intercellular communication analysis revealed defects in brain-derived neurotrophic factor (BDNF)-TrkB signaling cascade in old NSCs. Carboxypeptidase E (CPE) was found to be highly enriched in NSCs, and played a crucial role in mature/proBDNF balance and adult neurogenesis. Diminishment of CPE with aging resulted in impaired generation of BDNF, thus limiting the neurogenesis in old neurogenic niches. Restoring CPE expression markedly rescued the adult neurogenesis by increasing the production of mature BDNF, offering an attractive therapeutic strategy for the treatment of certain disorders in regions associated with constitutive neurogenesis.
Maternal obesity raises the risk of high-cholesterol exposure for their offspring. Studies in cohorts and animal models report that maternal obesity could increase the risk of neurodevelopmental disorders in offspring including intellectual disabilities and autism spectrum disorders (ASDs). However, whether exposure to high cholesterol is responsible for brain developmental defects, as well as its underlying mechanism, is still unclear. Here, we constructed a cholesterol exposure model utilizing human pluripotent stem cell (hPSC)-derived cerebral organoids by exogenously adding cholesterol into the culture system. We observed enlargement of endosomes, decreased neural progenitor proliferation, and premature neural differentiation in brain organoids with the treatment of cholesterol. Moreover, in comparison with published transcriptome data, we found that our single-cell sequencing results showed a high correlation with ASD, indicating that high cholesterol during maternal might mediate the increased risk of ASD in the offspring. Our results reveal a reduction of neural progenitor proliferation in a cholesterol exposure model, which might be a promising indicator for prenatal diagnosis and offer a dynamic human model for maternal environment exposure.