TGF-β对肿瘤微环境中免疫监视及细胞外基质的调控作用

转化生长因子β(transforming growth factorβ,TGF-β)是一种多功能的细胞因子,能够调控细胞增殖、分化、黏附、迁移及凋亡等行为,在胚胎发育过程和成体组织稳态维持中发挥重要的作用。而在许多疾病状态下,特别是在癌症中,TGF-β不仅能够影响肿瘤细胞的增殖与转移,其对于肿瘤微环境的调控与塑造也受到越来越多的关注。肿瘤微环境是指肿瘤在发生和发展过程中所处的内环境,由肿瘤细胞本身、相邻正常组织中的间质细胞,以及这些细胞所释放的众多细胞因子等共同组成。肿瘤微环境是肿瘤发展的重要机制,也是肿瘤临床治疗领域亟待探索的关键问题。TGF-β是调节肿瘤微环境组成和功能的主要参与者之一。在本综述中,将着重讨论TGF-β对于肿瘤微环境中的免疫监视机制及肿瘤细胞外基质的主要影响。即TGF-β对于构成先天性和获得性抗肿瘤免疫应答的各种类群的免疫细胞具有广泛的调控作用,从而削弱宿主的肿瘤免疫监视功能。同时,TGF-β通过促进肿瘤相关成纤维细胞的产生,以及肿瘤细胞外基质的纤维化,有助于肿瘤的恶变和转移。此外,还介绍了通过阻断肿瘤微环境中TGF-β信号通路进行肿瘤治疗的主要策略及独特优势。而未来进一步解析TGF-β信号在肿瘤微环境中的复杂调控作用,并建立有效的靶向干预方法对于开发高效的抗肿瘤药物具有重要的意义。     

Rainfall manipulation experiments as simulated by terrestrial biosphere models: Where do we stand?

Changes in rainfall amounts and patterns have been observed and are expected to continue in the near future with potentially significant ecological and societal consequences. Modelling vegetation responses to changes in rainfall is thus crucial to project water and carbon cycles in the future. In this study, we present the results of a new model‐data intercomparison project, where we tested the ability of 10 terrestrial biosphere models to reproduce the observed sensitivity of ecosystem productivity to rainfall changes at 10 sites across the globe, in nine of which, rainfall exclusion and/or irrigation experiments had been performed. The key results are as follows: (a) Inter‐model variation is generally large and model agreement varies with timescales. In severely water‐limited sites, models only agree on the interannual variability of evapotranspiration and to a smaller extent on gross primary productivity. In more mesic sites, model agreement for both water and carbon fluxes is typically higher on fine (daily–monthly) timescales and reduces on longer (seasonal–annual) scales. (b) Models on average overestimate the relationship between ecosystem productivity and mean rainfall amounts across sites (in space) and have a low capacity in reproducing the temporal (interannual) sensitivity of vegetation productivity to annual rainfall at a given site, even though observation uncertainty is comparable to inter‐model variability. (c) Most models reproduced the sign of the observed patterns in productivity changes in rainfall manipulation experiments but had a low capacity in reproducing the observed magnitude of productivity changes. Models better reproduced the observed productivity responses due to rainfall exclusion than addition. (d) All models attribute ecosystem productivity changes to the intensity of vegetation stress and peak leaf area, whereas the impact of the change in growing season length is negligible. The relative contribution of the peak leaf area and vegetation stress intensity was highly variable among models.     

Expansion of MIR482/2118 by a class‐II transposable element in cotton

Some plant microRNA (miRNA) families contain multiple members generating identical or highly similar mature miRNA variants. Mechanisms underlying the expansion of miRNA families remain elusive, although tandem and/or segmental duplications have been proposed. In this study of two tetraploid cottons, Gossypium hirsutum and Gossypium barbadense, and their extant diploid progenitors, Gossypium arboreum and Gossypium raimondii, we investigated the gain and loss of members of the miR482/2118 superfamily, which modulates the expression of nucleotide‐binding site leucine‐rich repeat (NBS‐LRR) disease resistance genes. We found significant expansion of MIR482/2118d in G. barbadense, G. hirsutum and G. raimondii, but not in G. arboreum. Several newly expanded MIR482/2118d loci have mutated to produce different miR482/2118 variants with altered target‐gene specificity. Based on detailed analysis of sequences flanking these MIR482/2118 loci, we found that this expansion of MIR482/2118d and its derivatives resulted from an initial capture of an MIR482/2118d by a class‐II DNA transposable element (TE) in G. raimondii prior to the tetraploidization event, followed by transposition to new genomic locations in G. barbadense, G. hirsutum and G. raimondii. The ‘GosTE’ involved in the capture and proliferation of MIR482/2118d and its derivatives belongs to the PIF/Harbinger superfamily, generating a 3‐bp target site duplication upon insertion at new locations. All orthologous MIR482/2118 loci in the two diploids were retained in the two tetraploids, but mutation(s) in miR482/2118 were observed across all four species as well as in different cultivars of both G. barbadense and G. hirsutum, suggesting a dynamic co‐evolution of miR482/2118 and its NBS‐LRR targets. Our results provide fresh insights into the mechanisms contributing to MIRNA proliferation and enrich our knowledge on TEs.     

Requirements for human embryonic stem cells

‘Requirements for Human Embryonic Stem Cells’ is the first set of guidelines on human embryonic stem cells in China, jointly drafted and agreed upon by experts from the Chinese Society for Stem Cell Research. This standard specifies the technical requirements, test methods, test regulations, instructions for use, labelling requirements, packaging requirements, storage requirements and transportation requirements for human embryonic stem cells, which is applicable to the quality control for human embryonic stem cells. It was originally released by the China Society for Cell Biology on 26 February 2019 and was further revised on 30 April 2020. We hope that publication of these guidelines will promote institutional establishment, acceptance and execution of proper protocols, and accelerate the international standardization of human embryonic stem cells for applications.     

Hyaluronate supports hESC‐cardiomyocyte cell therapy for cardiac regeneration after acute myocardial infarction

IntroductionEnormous progress has been made in cardiac regeneration using human embryonic stem cell‐derived cardiomyocyte (hESC‐CM) grafts in pre‐clinical trials. However, the rate of cell survival has remained very low due to anoikis after transplantation into the heart as single cells. Numerous solutions have been proposed to improve cell survival, and one of these strategies is to co‐transplant biocompatible materials or hydrogels with the hESC‐CMs.MethodsIn our study, we screened various combinations of biomaterials that could promote anoikis resistance and improve hESC‐CM survival upon co‐transplantation and promote cardiac functional recovery. We injected different combinations of Matrigel, alginate and hyaluronate with hESC‐CM suspensions into the myocardium of rat models with myocardial infarction (MI).ResultsOur results showed that the group treated with a combination of hyaluronate and hESC‐CMs had the lowest arrhythmia rates when stimulated with programmed electrical stimulation. While all three combinations of hydrogel‐hESC‐CM treatments improved rat cardiac function compared with the saline control group, the combination with hyaluronate most significantly reduced pathological changes from left ventricular remodelling and improved both left ventricular function and left ventricular ejection fraction by 28 days post‐infarction.ConclusionHence, we concluded that hyaluronate‐hESC‐CM is a superior combination therapy for promoting cardiac regeneration after myocardial infarction.