A double take on bivalent promoters

Histone modifications and chromatin-associated protein complexes are crucially involved in the control of gene expression, supervising cell fate decisions and differentiation. Many promoters in embryonic stem (ES) cells harbor a distinctive histone modification signature that combines the activating histone H3 Lys 4 trimethylation (H3K4me3) mark and the repressive H3K27me3 mark. These bivalent domains are considered to poise expression of developmental genes, allowing timely activation while maintaining repression in the absence of differentiation signals. Recent advances shed light on the establishment and function of bivalent domains; however, their role in development remains controversial, not least because suitable genetic models to probe their function in developing organisms are missing. Here, we explore avenues to and from bivalency and propose that bivalent domains and associated chromatin-modifying complexes safeguard proper and robust differentiation.     

拟胚体贴壁时间对小鼠胚胎干细胞心肌分化的影响

目的观察拟胚体(EB)贴壁时间对小鼠胚胎干细胞(ESC)心肌分化的影响并研究其机制。方法用悬滴培养法促进ESCs形成EBs。EBs在不同的分化天数贴壁,观察搏动EBs百分比,RT-PCR检测Nkx2.5,GATA4和β-MHC mRNA表达,Western blot检测Src家族酪氨酸激酶磷酸化水平。结果分化第3,4天贴壁组搏动EB百分比及Nkx2.5,GATA4,β-MHC表达水平显著低于分化第5,6和7天贴壁组(P<0.05);EB贴壁能够使Src激酶磷酸化水平升高,Src激酶阻断剂PP2能够抑制贴壁诱发的Src激酶磷酸化水平升高(P<0.05);对于分化第4天贴壁组,在分化第4～6天使用PP2能够增加搏动EBs百分比及β-MHC表达水平(P<0.05)。结论 EB贴壁时间是影响ESC心肌分化的一个重要因素。在分化第4天或者之前贴壁可以显著抑制心肌分化,其机制可能是EB贴壁激活了Src激酶。     

Antitumor Effect of Embryonic Stem Cells in a Non-Small Cell Lung Cancer Model: Antitumor Factors and Immune Responses

Research in recent years has revealed that embryonic stem cells (ESCs) could generate obvious antitumor effects in both vitro and vivo. In vitro, ESCs could secrete soluble factors that are capable of blocking cancer cells proliferation, moreover, embryonic microenvironments could effectively inhibit tumorigenesis and metastasis; while in vivo, administration of ESCs in tumor-bearing mice could generate significant antitumor effects by indirectly activating the antitumor immune system. In this study, non-small cell lung cancer cells (Lewis Lung Carcinoma cells, LLCs) and ESCs were co-injected together into mice, after that subcutaneous tumor growth was monitored, cellular and humoral immune responses were detected, and different control groups were set to compare the results in different conditions. Our results suggested that compared to be injected alone, ESCs co-injected with cancer cells could inhibit cancer cell growth more efficiently in vivo, with more CD8+ lymphocytes generated in both peripheral circulation and spleen, and with higher serum anticancer cytokine level (interleukin (IL)-2 and interferon (IFN)-γ). We conclude that the boosted antitumor effects induced by ESCs and cancer cells co-injection may be both the effects of antitumor factors secreted by ESCs and immune responses induced by ESCs in vivo.     

Complementary functions of ATM and H2AX in development and suppression of genomic instability

Upon DNA damage, histone H2AX is phosphorylated by ataxia-telangiectasia mutated (ATM) and other phosphoinositide 3-kinase-related protein kinases. To elucidate further the potential overlapping and unique functions of ATM and H2AX, we asked whether they have synergistic functions in the development and maintenance of genomic stability by inactivating both genes in mouse germ line. Combined ATM/H2AX deficiency caused embryonic lethality and dramatic cellular genomic instability. Mechanistically, severe genomic instability in the double-deficient cells is associated with a requirement for H2AX to repair oxidative DNA damage resulting from ATM deficiency. We discuss these findings in the context of synergies between ATM and other repair factors.     

百草枯中毒的研究进展

随着百草枯(PQ)的广泛应用,PQ中毒事件数量逐年增加,已成为我国第二位的农药中毒事件。PQ对人有剧毒,中毒后致多脏器严重损害,病死率极高,其中毒机制尚不完全明确,氧自由基产生学说为大多数学者认可。PQ中毒暂无特效解毒药,临床上主要采取综合治疗的办法,如洗胃、导泻、吸附体内毒素、应用激素及免疫抑制剂、清除氧自由基、保护各脏器功能等,同时结合有效的血液净化手段,本文旨在对相关进展做一简要综述。     

Reverse engineering the mechanical and molecular pathways in stem cell morphogenesis

The formation of relevant biological structures poses a challenge for regenerative medicine. During embryogenesis, embryonic cells differentiate into somatic tissues and undergo morphogenesis to produce three‐dimensional organs. Using stem cells, we can recapitulate this process and create biological constructs for therapeutic transplantation. However, imperfect imitation of nature sometimes results in in vitro artifacts that fail to recapitulate the function of native organs. It has been hypothesized that developing cells may self‐organize into tissue‐specific structures given a correct in vitro environment. This proposition is supported by the generation of neo‐organoids from stem cells. We suggest that morphogenesis may be reverse engineered to uncover its interacting mechanical pathway and molecular circuitry. By harnessing the latent architecture of stem cells, novel tissue‐engineering strategies may be conceptualized for generating self‐organizing transplants. Copyright © 2013 John Wiley & Sons, Ltd.     

两种硫辛酸对映体对胚胎体外发育的影响

目的：探讨(R)-硫辛酸和(S)-硫辛酸对胚胎体外发育的影响。方法解冻复苏卵裂期胚胎,分别在含不同浓度(R)-硫辛酸和(S)-硫辛酸的GⅡ培养基微滴中培养,观察各组的桑胚率、致密化率、囊胚率和优质囊胚率。结果硫辛酸可提高胚胎体外发育率,(R)-硫辛酸浓度10×10-9 mol/m3组桑胚率、致密化率、囊胚率和优质囊胚率分别达到了59.2%,55.1%,49.0%和54.2%,均高于其他浓度组（P<0.01）。(R)-硫辛酸浓度10×10-9 mol/m3组的桑胚率、致密化率和优质胚胎率均高于(S)-硫辛酸10×10-9 mol/m3组（P<0.05）。结论硫辛酸对胚胎体外发育具有促进作用,特别是对桑胚率和囊胚率具有显著的影响。(R)-硫辛酸10×10-9 mol/m3组的效果最好。