Self-renewal made simple

Embryonic stem cells (ESCs) are prone to differentiation in culture, suggesting that maintenance of the pluripotent state must be actively induced. In a recent issue of Nature, Ying et al. (2008) use soluble small molecules to inhibit pro-differentiation signals and reveal ESC self-renewal as a default cell fate.     

上皮间质转化与干细胞自我更新和分化

上皮间质转化(epithelial-mesenchymal transition,EMT)是指上皮细胞失去连接和极性转变为间质细胞的过程,这一现象普遍存在于胚胎发育、创伤愈合、器官纤维化以及肿瘤转移.在胚胎早期发育和晚期发育过程,例如着床、原肠运动、心血管发育等事件中有EMT和间质上皮转化(mesenchymal-ep...     

Cdk6在维持ES细胞自我更新中的作用

细胞周期蛋白依赖性激酶6（cyclin dependent kinase 6,Cdk6）对胚胎早期发育有着重要的作用.然而,它在胚胎干（embryonic stem,ES）细胞中的生物学功能仍不清楚.在该研究中,我们运用RNA干扰技术和基因表达分析方法探索了Cdk6在小鼠胚胎干细胞中的功能及分子机制.结果表明：Cdk6的表达水平与小鼠ES细胞的自我更新密切相关.首先,维甲酸（RA）处理和白血病抑制因子（LIF）去除实验显示 ,随着ES细胞的分化,Cdk6的表达水平明显降低.更为重要的是,RNA干扰介导的Cdk6表达抑制导致ES细胞自我更新相关基因的显著下调,同时伴随细胞分化基因的表达激活,提示Cdk6对维持ES细胞自我更新至关重要.     

Self-renewal and lineage restriction of hematopoietic stem cells

Over the past decade, the purification and characterization of hematopoietic stem cells have ascertained their presence at the clonal level although they had hitherto existed conceptually. Now we have begun to understand their functions in molecular terms. Several important works indicative of such a new era in stem cell biology have been published recently. In particular, Bmi1, which belongs to the Polycomb group of genes, has been implicated as one of the basic molecules to maintain the proliferation capacity in hematopoietic stem cells. We need to seek other similarly important molecules for their functions. Perhaps studying interactions among genes is one of the most exciting subjects in stem cell research.     

Zfx基因与干细胞自我更新

干细胞具有自我更新保持不分化状态的特性,不同的干细胞具有不同的自我更新机制. Zfx基因(zinc fin ger-X gene)在部分胚胎干细胞和造血干细胞中高表达,该基因高表达有利于胚胎干细胞和造血干细胞自我更新; Zfx基因表达不足或缺乏的胚胎干细胞和造血干细胞自我更新的能力下降,细胞凋亡明显增加.在胚胎干细胞和造血干细胞中发现一些Zfx基因直接调控的靶基因,Zfx 基因可能是控制各种干细胞自我更新的共同的分子机制. Zfx基因表达不足不影响胚胎干细胞和造血干细胞的分化,缺乏 Zfx基因的胚胎干细胞和造血干细胞能够正常分化为各自的功能细胞.     

哺乳动物精原干细胞自我更新调控的研究进展

精原干细胞（spermatogonial stem cells,SSCs）具有自我更新和分化的功能,这两种功能的平衡协调不仅能维持其自身数量的稳定,还能满足雄性动物精子生成的需要。近几年,由于细胞培养技术、基因工程技术、生殖细胞移植技术的建立和完善,使SSCs自我更新调控机制的研究取得了许多突破,主要体现在蛋白调控因子和微小RNA分子以及DNA甲基化新作用的发现等方面。该文将着重围绕调控SSCs自我更新的外源性细胞因子和内源性转录因子等蛋白因子进行综述,以期为哺乳动物SSCs的深入研究提供借鉴。     

Self-renewal vs. differentiation of mouse embryonic stem cells

Embryonic stem (ES) cells are typically derived from the inner cell mass of the preimplantation blastocyst and can both self-renew and differentiate into all the cells and tissues of the embryo. Because they are pluripotent, ES cells have been used extensively to analyze gene function in development via gene targeting. The embryonic stem cell is also an unsurpassed starting material to begin to understand a critical, largely inaccessible period of development. If their differentiation could be controlled, they would also be an important source of cells for transplantation to replace cells lost through disease or injury or to replace missing hormones or genes. Traditionally, ES cells have been differentiated in suspension culture as embryoid bodies, named because of their similarity to the early postimplantation-staged embryo. Unlike the pristine organization of the early embryo, differentiation in embryoid bodies appears to be largely unpatterned, although multiple cell types form. It has recently been possible to separate the desired cell types from differentiating ES cells in embryoid bodies by using cell-type-restricted promoters driving expression of either antibiotic resistance genes or fluorophores such as EGFP. In combination with growth factor exposure, highly differentiated cell types have successfully been derived from ES cells. Recent technological advances such as RNA interference to knock down gene expression in ES cells are also producing enriched populations of cells and elucidating gene function in early development.     

维持胚胎干细胞自我更新分子机制的研究进展

胚胎干细胞通过特殊内源性分子的表达,以及微环境中多种细胞因子和胞外基质的刺激,构成信号网络,共同调控自我更新.近年来,通过对Oct3/4、Nanog等胚胎干细胞特殊分子标记,以及LIF-STAT3,Wnt-β-连环素,BMP-Id等信号通路的研究,探讨了胚胎干细胞自我更新信号网络的分子机制.维持自我更新的关键在于胚胎干细胞生长微环境中的各种细胞因子和胞外基质的含量,以及细胞内源性特异分子表达量之间的平衡.     

维持胚胎干细胞自我更新状态的分子信号途径

胚胎干细胞是从胚胎植入前期胚泡内细胞团分离的细胞,可以长久维持对称性自我更新的未分化状态。多种胞内外细胞因子介导的信号途径参与这种状态的调节。现对胚胎干细胞自我更新途径分子机制进行综述,并提出有待进一步阐明的相关问题。     

Self-renewal and differentiation capacity of young and aged stem cells

Because of their ability to self-renew and differentiate, adult stem cells are the in vivo source for replacing cells lost on a daily basis in high turnover tissues during the life of an organism. Adult stem cells however, do suffer the effects of aging resulting in decreased ability to self-renew and properly differentiate. Aging is a complex process and identification of the mechanisms underlying the aging of (stem) cell population(s) requires that relatively homogenous and well characterized populations can be isolated. Evaluation of the effect of aging on one such adult stem cell population, namely the hematopoietic stem cell (HSC), which can be purified to near homogeneity, has demonstrate that they do suffer cell intrinsic age associated changes. The cells that support HSC, namely marrow stromal cells, or mesenchymal stem cells (MSC), may similarly be affected by aging, although the inability to purify these cells to homogeneity precludes definitive assessment. As HSC and MSC are being used in cell-based therapies clinically, improved insight in the effect of aging on these two stem cell populations will probably impact the selection of sources for these stem cells.     

Imaging mitophagy in the fruit fly

Loss-of-function mutations in the genes encoding PRKN/parkin and PINK1 cause autosomal recessive Parkinson disease (PD). Seminal work in Drosophila revealed that loss of park/parkin and Pink1 causes prominent mitochondrial pathology in flight muscle and, to a lesser extent, in dopaminergic neurons. Subsequent studies in cultured mammalian cells discovered a crucial role for PRKN/PARK2 and PINK1 in selective macroautophagic removal of mitochondria (mitophagy). However, direct evidence for the existence of a PINK1-PRKN/PARK2-mediated mitophagy pathway in vivo is still scarce. Recently, we engineered Drosophila that express the mitophagy reporter mt-Keima. We demonstrated that mitophagy occurs in flight muscle cells and dopaminergic neurons in vivo and increases with aging. Moreover, this age-dependent rise depends on park and Pink1. Our data also suggested that some aspects of the mitochondrial phenotype of park- and Pink1-deficient flies are independent of the mitophagy defect, and that park and Pink1 may have multiple functions in the regulation of the integrity of these organelles. Here, we discuss implications of these findings as well as possible future applications of the mt-Keima fly model.