Cell Regeneration最新文献

Adult neurogenesis is a unique cellular process of the ongoing generation of new neurons throughout life, which primarily occurs in the subgranular zone (SGZ) of the dentate gyrus (DG) and the subventricular zone (SVZ) of the lateral ventricle. In the adult DG, newly generated granule cells from neural stem cells (NSCs) integrate into existing neural circuits, significantly contributing to cognitive functions, particularly learning and memory. Recently, more and more studies have shown that rather than being a homogeneous population of identical cells, adult NSCs are composed of multiple subpopulations that differ in their morphology and function. In this study, we provide an overview of the origin, regional characteristics, prototypical morphology, and molecular factors that contribute to NSC heterogeneity. In particular, we discuss the molecular mechanisms underlying the balance between activation and quiescence of NSCs. In summary, this review highlights that deciphering NSC heterogeneity in the adult brain is a challenging but critical step in advancing our understanding of tissue-specific stem cells and the process of neurogenesis in the adult brain.

Intestinal homeostasis relies on the continuous renewal of intestinal stem cells (ISCs), which could be epigenetically regulated. While protein arginine methyltransferase 5 (Prmt5) is known to play a key role in multiple organs as an epigenetic modifier, its specific function in maintaining intestinal homeostasis remains to be elucidated. Here, we show that Prmt5 is highly expressed in mouse crypts. The deletion of Prmt5 results in ISCs deficiency, ectopic localization of Paneth cells, and spontaneous colitis. Mechanistically, Prmt5 sustains a high level of H3K27ac accumulation by inhibiting Hdac9 expression in the intestinal epithelium, and maintains the stemness of ISCs in a cell-autonomous manner. Notably, inhibition of histone deacetylases can rescue both self-renewal and differentiation capacities of Prmt5-depleted ISCs. These findings highlight Prmt5 as a critical regulator in intestinal epithelium development and tissue homeostasis.

Salivary gland stem/progenitor cells (SSPCs) hold significant potential for regenerative medicine, especially for patients suffering from salivary gland dysfunction due to various causes such as radiation therapy, Sjögren's syndrome, and aging. This review provides a comprehensive overview of SSPCs, including their characteristics, isolation, culture techniques, differentiation pathways, and their role in tissue regeneration. Additionally, we highlight recent advances in cell- and tissue-based therapies, such as SSPC transplantation and bioengineered organ replacements. The challenges in translating SSPC research into effective clinical therapies are also discussed, alongside proposed solutions and future research directions.

The cultivation and differentiation of human embryonic stem cells (hESCs) into organoids are crucial for advancing of new drug development and personalized cell therapies. Despite establishing of chemically defined hESC culture media over the past decade, these media's reliance on growth factors, which are costly and prone to degradation, poses a challenge for sustained and stable cell culture. Here, we introduce an hESC culture system(E6Bs) that facilitates the long-term, genetically stable expansion of hESCs, enabling cells to consistently sustain high levels of pluripotency markers, including NANOG, SOX2, TRA-1-60, and SSEA4, across extended periods. Moreover, organoids derived from hESCs using this medium were successfully established and expanded for at least one month, exhibiting differentiation into cortical organoids, GABAergic precursor organoids and heart-forming organoids. This innovative system offers a robust tool for preserving hESC homeostasis and modeling the nervous system in vitro.

Organoid technology provides a transformative approach to understand human physiology and pathology, offering valuable insights for scientific research and therapeutic development. Human gastric organoids, in particular, have gained significant interest for applications in disease modeling, drug discovery, and studies of tissue regeneration and homeostasis. However, the lack of standardized quality control has limited their extensive clinical applications. The "Human Gastric Organoids" is part of a series of guidelines for human gastric organoids in China, which establishes comprehensive standards on terminology, technical specifications, testing methods, inspection rules, usage instructions, labeling, transportation, and storage, developed by experts from the Chinese Society for Cell Biology and its branch societies. Released on October 29, 2024, this guideline aims to establish standardized protocols, enhance institutional practices, and promote international standardization for clinical and research applications of human gastric organoids.

Astroglia are integral to brain development and the emergence of neurodevelopmental disorders. However, studying the pathophysiology of human astroglia using brain organoid models has been hindered by inefficient astrogliogenesis. In this study, we introduce a robust method for generating astroglia-enriched organoids through BMP4 treatment during the neural differentiation phase of organoid development. Our RNA sequencing analysis reveals that astroglia developed within these organoids exhibit advanced developmental characteristics and enhanced synaptic functions compared to those grown under traditional two-dimensional conditions, particularly highlighted by increased neurexin (NRXN)-neuroligin (NLGN) signaling. Cell adhesion molecules, such as NRXN and NLGN, are essential in regulating interactions between astroglia and neurons. We further discovered that brain organoids derived from human embryonic stem cells (hESCs) harboring the autism-associated NLGN3 R451C mutation exhibit increased astrogliogenesis. Notably, the NLGN3 R451C astroglia demonstrate enhanced branching, indicating a more intricate morphology. Interestingly, our RNA sequencing data suggest that these mutant astroglia significantly upregulate pathways that support neural functions when compared to isogenic wild-type astroglia. Our findings establish a novel astroglia-enriched organoid model, offering a valuable platform for probing the roles of human astroglia in brain development and related disorders.

Gastric cancer is one of the most common malignancies with poor prognosis. The use of organoids to simulate gastric cancer has rapidly developed over the past several years. Patient-derived gastric cancer organoids serve as in vitro models that closely mimics donor characteristics, offering new opportunities for both basic and applied research. The "Human Gastric Cancer Organoid" is part of a series of guidelines for human gastric cancer organoids in China, jointly drafted by experts from the Chinese Society for Cell Biology and its branches, and initially released on October 29, 2024. This standard outlines terminology, technical requirements, assessment protocols, and applies to production, evaluation procedures, and quality control for human gastric cancer organoids. The publication of this guideline aims to assist institutions in endorsing, establishing, and applying best practices, advancing the international standardization of human gastric cancer organoids for clinical development and therapeutic application.

Peripheral nerve injury (PNI) usually causes severe motor, sensory and autonomic dysfunction. In addition to direct surgical repair, rehabilitation exercises, and traditional physical stimuli, for example, electrical stimulation, have been applied in promoting the clinical recovery of PNI for a long time but showed low efficiency. Recently, significant progress has been made in new physical modulation to promote peripheral nerve regeneration. We hereby review current progress on the mechanism of peripheral nerve regeneration after injury and summarize the new findings and evidence for the application of physical modulation, including electrical stimulation, light, ultrasound, magnetic stimulation, and mechanical stretching in experimental studies and the clinical treatment of patients with PNI.

Regenerative responses are particularly important in the lungs, which are critical for gas exchange and frequently challenged by environmental insults. The lung progenitor cells play a central role in the lung regeneration response, and their dysfunction is associated with various lung diseases. Understanding the mechanisms regulating lung progenitor cell function is essential for developing new therapeutic approaches to promote lung regeneration. This review summarizes recent advancements in the field of lung regeneration, focusing on the metabolic control of lung progenitor cell function. We discuss cell lineage plasticity and cell-cell signaling under different physiological conditions. Additionally, we highlight the connection between progenitor cell dysfunction and lung diseases, emphasizing the need to develop new therapeutic strategies in regenerative medicine to improve lung regenerative capacity.

In zebrafish, Müller glia (MG) cells retain the ability to proliferate and de-differentiate into retinal progenitor-like cells, subsequently differentiating into retinal neurons that can replace those damaged or lost due to retinal injury. In contrast, the reprogramming potential of MG in mammals has been lost, with these cells typically responding to retinal damage through gliosis. Considerable efforts have been dedicated to achieving the reprogramming of MG cells in mammals. Notably, significant advancements have been achieved in reprogramming MG cells in mice employing various methodologies. At the same time, some inevitable challenges have hindered identifying accurate MG cell reprogramming rather than the illusion, let alone improving the reprogramming efficiency and maturity of daughter cells. Recently, several strategies, including lineage tracking, multi-omics techniques, and functional analysis, have been developed to investigate the MG reprogramming process in mice. This review summarizes both the advantages and limitations of these novel strategies for analyzing MG reprogramming in mice, offering insights into enhancing the reliability and efficiency of MG reprogramming.