摘要: Neurogenesis is the process of generating new neurons from neural stem cells (NSCs) and plays a crucial role in neurological diseases. The process involves a series of steps, including NSC proliferation, migration and differentiation, which are regulated by multiple pathways such as neurotrophic Trk and fibroblast growth factor receptors (FGFR) signalling. Despite the discovery of numerous compounds capable of modulating individual stages of neurogenesis, it remains challenging to identify an agent that can regulate multiple cellular processes of neurogenesis. Here, through screening of bioactive compounds in dietary functional foods, we identified a flavonoid chrysin that not only enhanced the human NSCs proliferation but also facilitated neuronal differentiation and neurite outgrowth. Further mechanistic study revealed the effect of chrysin was attenuated by inhibition of neurotrophic tropomyosin receptor kinase-B (TrkB) receptor. Consistently, chrysin activated TrkB and downstream ERK1/2 and AKT. Intriguingly, we found that the effect of chrysin was also reduced by FGFR1 blockade. Moreover, extended treatment of chrysin enhanced levels of brain-derived neurotrophic factor, as well as FGF1 and FGF8. Finally, chrysin was found to promote neurogenesis in human cerebral organoids by increasing the organoid expansion and folding, which was also mediated by TrkB and FGFR1 signalling. To conclude, our study indicates that activating both TrkB and FGFR1 signalling could be a promising avenue for therapeutic interventions in neurological diseases, and chrysin appears to be a potential candidate for the development of such treatments. In this study, we found a dietary flavonoid, chrysin, cooperatively activated tropomyosin receptor kinase-B and FGFR1 signalling with up-regulation of their endogenous ligands to promote human neurogenesis. image

摘要: The above article, published online on 19 May 2024 in Wiley Online Library (), has been retracted by agreement between the authors; the journal Deputy Editor, Yunfeng Lin; and John Wiley & Sons Ltd. Following additional research, the authors observed results that called into question their original findings. The retraction has been agreed due to a lack of sufficient data to support the article's conclusion.

摘要: The presence of extensive infiltrated macrophages with impaired phagocytosis is widely recognised as a significant regulator for the development of endometriosis (EMs). Nevertheless, the metabolic characteristics and the fundamental mechanism of impaired macrophage phagocytosis are yet to be clarified. Here, we observe that there is the decreased expression of haematopoietic cellular kinase (HCK) in macrophage of peritoneal fluid from EMs patients, which might be attributed to high oestrogen and hypoxia condition. Of note, HCK deficiency resulted in impaired macrophage phagocytosis, and increased number and weight of ectopic lesions in vitro and in vivo. Mechanistically, this process was mediated via regulation of glutamine metabolism, and further upregulation of macrophage autophagy in a c-FOS/c-JUN dependent manner. Additionally, macrophages of EMs patients displayed insufficient HCK, excessive autophagy and phagocytosis dysfunction. In therapeutic studies, supplementation with glutamine-pre-treated macrophage or Bafilomycin A1 (an autophagy inhibitor)-pre-treated macrophage leads to the induction of macrophage phagocytosis and suppression of EMs development. This observation reveals that the aberrant HCK-glutamine-autophagy axis results in phagocytosis obstacle of macrophage and further increase the development risk of Ems. Additionally, it offers potential therapeutic approaches to prevent EMs, especially patients with insufficient HCK and macrophage phagocytosis dysfunction.

摘要: Major zygotic genome activation (ZGA) occurs at the late 2-cell stage and involves the activation of thousands of genes, supporting early embryonic development. The reasons underlying the regulation of ZGA are not clear. Acetylation modifications of histone tails promote transcriptional activation, and the maternal deletion of H4K16ac leads to failure in ZGA. GATAD2B is one of the core subunits of the nucleosome remodelling and histone deacetylation (NuRD) complex. Our research has shown that GATAD2B exhibits specific nucleus localization and high protein expression from the late 2-cell stage to the 8-cell stage. This intriguing phenomenon prompted us to investigate the relationship between GATAD2B and the ZGA. We discovered a distinctive pattern of GATAD2B, starting from the late 2-cell stage with nuclear localization. GATAD2B depletion resulted in defective embryonic development, including increased DNA damage at morula, decreased blastocyst formation rate, and abnormal differentiation of ICM/TE lineages. Consistent with the delay during the cleavage stage, the transcriptome analysis of the 2-cell embryo revealed inhibition of the cell cycle G2/M phase transition pathway. Furthermore, the GATAD2B proteomic data provided clear evidence of a certain association between GATAD2B and molecules involved in the cell cycle pathway. As hypothesized, GATAD2B-deficient 2-cell embryos exhibited abnormalities in ZGA during the maternal-to-embryonic transition, with lower expression of the major ZGA marker MERVL. Overall, our results demonstrate that GATAD2B is essential for early embryonic development, in part through facilitating ZGA.

摘要: DNA nanostructures, known for their programmability, ease of modification, and favourable biocompatibility, have gained widespread application in the biomedical field. Among them, Tetrahedral DNA Origami (TDOs), as a novel DNA nanostructure, possesses well-defined structures, multiple modification sites, and large cavities, making it a promising drug carrier. However, current understanding of TDOs' interactions with biological systems, particularly with target cells and organs, remains unexplored, limiting its further applications in biomedicine. In this work, we prepared TDOs with an average particle size of 40 nm and labelled them with Cy5 fluorescent molecules. Following intravenous injection in mice, the uptake of TDOs by different types of liver and kidney cells was observed. Results indicated that TDOs accumulate in renal tubules and are metabolized by Kupffer cells, epithelial cells, and hepatocytes in the liver. Additionally, in a tumour-bearing mouse model, TDOs passively targeted tumour tissues and exhibited excellent tumour penetration and retention after rapid metabolism in hepatocytes. Our findings provide crucial insights for the development of TDO-based drug delivery systems.

摘要: Ischemic heart disease, especially myocardial infarction (MI), is one of the leading causes of death worldwide, and desperately needs effective treatments, such as cell therapy. Cardiopulmonary progenitors (CPPs) are stem cells for both heart and lung, but their repairing role in damaged heart is still unknown. Here, we obtained CPPs from E9.5 mouse embryos, maintained their stemness while expanding, and identified their characteristics by scRNA-seq, flow cytometry, quantitative reverse transcription-polymerase chain reaction, and differentiation assays. Moreover, we employed mouse MI model to investigate whether CPPs could repair the injured heart. Our data identified that CPPs exhibit hybrid fibroblastic, endothelial, and mesenchymal state, and they could differentiate into cell lineages within the cardiopulmonary system. Moreover, intramyocardial injection of CPPs improves cardiac function through CPPs exosomes (CPPs-Exo) by promotion of cardiomyocytic proliferation and vascularization. To uncover the underlying mechanism, we used miRNA-seq, bulk RNA-seq, and bioinformatic approaches, and found the highly expressed miR-27b-3p in CPPs-Exo and its target gene Sik1, which can influence the transcriptional activity of CREB1. Therefore, we postulate that CPPs facilitate cardiac repair partially through the SIK1-CREB1 axis via exosomal miR-27b-3p. Our study offers a novel insight into the role of CPPs-Exo in heart repair and highlights the potential of CPPs-Exo as a promising therapeutic strategy for MI.

摘要: 'Requirements for Human Natural Killer Cells' is the latest set of guidelines on human NK cells in China, jointly drafted and agreed upon by experts from the Standards Committee of Chinese Society for Cell Biology. This standard specifies requirements for the human natural killer (NK) cells, including the technical requirements, test methods, test regulations, instructions for use, labeling requirements, packaging requirements, storage and transportation requirements, and waste disposal requirements of NK cells. This standard is applicable for the quality control of NK cells, derived from human tissues, or differentiated/transdifferentiated from stem cells. It was originally released by the Chinese Society for Cell Biology on 30 August, 2022. We hope that the publication of these guidelines will promote institutional establishment, acceptance, and execution of proper protocols and accelerate the international standardization of human NK cells for applications.

摘要: It is well recognized that mitochondrial dynamics plays a vital role in cartilage physiology. Any perturbation in mitochondrial dynamics could cause disorders in cartilage metabolism and even lead to the occurrence of cartilage diseases such as osteoarthritis (OA). TGF-beta 3, as an important growth factor that appears in the joints of OA disease, shows its great potential in chondrocyte growth and metabolism. Nevertheless, the role of TGF-beta 3 on mitochondrial dynamics is still not well understood. Here we aimed to investigate the effect of TGF-beta 3 on mitochondrial dynamics of chondrocytes and reveal its underlying bio-mechanism. By using transmission electron microscopy (TEM) for the number and morphology of mitochondria, western blotting for the protein expressions, immunofluorescence for the cytoplasmic distributions of proteins, and RNA sequencing for the transcriptome changes related to mitochondrial dynamics. We found that TGF-beta 3 could increase the number of mitochondria in chondrocytes. TGF-beta 3-enhanced mitochondrial number was via promoting the mitochondrial fission. The mitochondrial fission induced by TGF-beta 3 was mediated by AMPK signaling. TGF-beta 3 activated canonical p-Smad3 signaling and resultantly mediated AMPK-induced mitochondrial fission. Taken together, these results elucidate an understanding of the role of TGF-beta 3 on mitochondrial dynamics in chondrocytes and provide potential cues for therapeutic strategies in cartilage injury and OA disease in terms of energy metabolism.

摘要: Human midbrain dopaminergic progenitors (mDAPs) are one of the most representative cell types in both basic research and clinical applications. However, there are still many challenges for the preparation and quality control of mDAPs, such as the lack of standards. Therefore, the establishment of critical quality attributes and technical specifications for mDAPs is largely needed. Human midbrain dopaminergic progenitor jointly drafted and agreed upon by experts from the Chinese Society for Stem Cell Research, is the first guideline for human mDAPs in China. This standard specifies the technical requirements, test methods, inspection rules, instructions for usage, labelling requirements, packaging requirements, storage requirements, transportation requirements and waste disposal requirements for human mDAPs, which is applicable to the quality control for human mDAPs. It was originally released by the China Society for Cell Biology on 30 August 2022. We hope that the publication of this guideline will facilitate the institutional establishment, acceptance and execution of proper protocols, and accelerate the international standardization of human mDAPs for clinical development and therapeutic applications.

摘要: Scaffold protein AF4/FMR2 family member 4 (AFF4) has been found to play a role in osteogenic commitment of stem cells. However, function of AFF4 in human periodontal ligament stem cells (hPDLSCs) has not been studied yet. This present study aims to investigate the biological effect of AFF4 on osteogenic differentiation of hPDLSCs and potential mechanistic pathway. First, AFF4 expression profile was evaluated in conditions of periodontitis and osteogenic differentiation of hPDLSCs by immunohistochemical staining, western blot and qRT-PCR. Next, si-RNA mediated knockdown and lentiviral transduction mediated overexpression of AFF4 were adopted to explore impact of AFF4 on osteogenic capacity of hPDLSCs. Then, possible mechanistic pathway was identified. At last, pharmacological agonist of autophagy, rapamycin, was utilized to affirm the role of autophagy in AFF4-regulated osteogenesis of hPDLSCs. First, AFF4 expressions were significantly lower in inflamed periodontal tissues and lipopolysaccharides-treated hPDLSCs than controls, and were up-regulated during osteogenic differentiation of hPDLSCs. Next, osteogenic potential of hPDLSCs was impaired by AFF4 knockdown and potentiated by AFF4 overexpression. Moreover, AFF4 was found to positively regulate autophagic activity in hPDLSCs. At last, rapamycin treatment was shown to be able to partly restore AFF4 knockdown-suppressed osteogenic differentiation. Our study demonstrates that AFF4 regulates osteogenic potential of hPDLSCs via targeting autophagic activity. The involvement of AFF4 in periodontal homeostasis was identified for the first time. The present study shows that AFF4 protein expression was significantly lower in periodontitis tissues than healthy periodontal tissues. And we further revealed that AFF4 regulates osteogenic differentiation of hPDLSCs. The above findings provide a clue for possible engagement of AFF4 in local dyshomeostasis in periodontitis.image