Organization of haemopoietic stem cells: the generation-age hypothesis.

This paper proposes that the previous division history of each stem cell is one determinant of the functional organization of the haemopoietic stem cell population. Stem cells from a lineage of stem cells which have generated many stem cells (older stem cells) are used in the animal to form blood before stem cells which have generated few stem cells (younger stem cells). The stem cell generating capacity of a lineage of stem cells is finite. After a given number of generations a stem cell is lost to the stem cell compartment by forming two committed precursors of the cell lines. Its part in blood formation is taken by the next oldest stem cell. We have called this proposal the generation-age hypothesis. Experimental evidence in support of the proposal is presented. We stripped away older stem cells from normal bone marrow and 13 day foetal liver with phase-specific drugs and revealed a younger population of stem cells whose capacity for stem cell generation was three- to four-fold greater than that of the average normal, untreated population. We aged normal stem cells by continuous irradiation and serial retransplantation and found that their stem cell generative capacity had declined eight-fold. We measured the stem cell generative capacity of stem cells in the bloodstream. It was a half to a quarter that of normal bone marrow stem cells and we found a subpopulation of circulating stem cells whose capacity for stem cell generation was an eighth to a fortieth that of normal femoral stem cells. This subpopulation was identified by its failure to express the brain-associated antigen which was present on 75% of normal femoral stem cells but was not found on their progeny, the committed precursors of granulocytes.     

ORGANIZATION OF HAEMOPOIETIC STEM CELLS: THE GENERATION-AGE HYPOTHESIS

This paper proposes that the previous division history of each stem cell is one determinant of the functional organization of the haemopoietic stem cell population. Stem cells from a lineage of stem cells which have generated many stem cells (older stem cells) are used in the animal to form blood before stem cells which have generated few stem cells (younger stem cells). The stem cell generating capacity of a lineage of stem cells is finite. After a given number of generations a stem cell is lost to the stem cell compartment by forming two committed precursors of the cell lines. Its part in blood formation is taken by the next oldest stem cell. We have called this proposal the generation-age hypothesis. Experimental evidence in support of the proposal is presented. We stripped away older stem cells from normal bone marrow and 12 day foetal liver with phase-specific drugs and revealed a younger population of stem cells whose capacity for stem cell generation was three- to four-fold greater than that of the average normal, untreated population. We aged normal stem cells by continuous irradiation and serial retransplantation and found that their stem cell generative capacity had declined eight-fold. We measured the stem cell generative capacity of stem cells in the bloodstream. It was a half, to a quarter that of normal bone marrow stem cells and we found a subpopulation of circulating stem cells whose capacity for stem cell generation was an eighth to a fortieth that of normal femoral stem cells. This subpopulation was identified by its failure to express the brain-associated antigen which was present on 75% of normal femoral stem cells but was not found on their progeny, the committed precursors of granulocytes.     

果蝇干细胞研究进展

本文主要介绍了果蝇五种干细胞,包括生殖干细胞、神经干细胞、造血干细胞、小肠干细胞、肾干细胞及其微环境（niche）的组成成份;简述了五种干细胞系统对应的分子标记;最后重点介绍了调控每种干细胞系统的信号通路。     

干细胞巢研究进展

干细胞巢即干细胞周围的微环境构成,一般包括干细胞的相邻细胞、粘附分子及基质等,但不同的干细胞有不同的巢结构。干细胞巢通过不同信号途径调控着干细胞的行为,使干细胞的自我更新和分化处于平衡状态。根据近年来有关干细胞巢的研究,本文从果蝇生殖系干细胞巢、哺乳动物造血干细胞巢、肠干细胞巢、毛囊表皮干细胞巢和神经干细胞巢等五个系统分别综述了干细胞巢的构成及其对干细胞的调节作用,探讨了干细胞巢作用于干细胞的内在机制。     

江西常绿阔叶林木本植物不同冠层高度当年生小枝茎构型对叶生物量的影响

以江西阳际峰自然保区69种木本植物为对象,采用标准化主轴回归(SMA)的方法,对不同冠层高度当年生小枝的构件生物量(叶生物量、茎生物量、小枝生物量)与茎构型特征(茎直径、茎长度、茎宽长比、茎体积和茎密度)进行了分析,研究当年生小枝茎构型对叶生物量的影响.结果表明:不同冠层高度及生活型间叶生物量、茎生物量、小枝生物量、茎直径、茎长度、茎宽长比及茎体积均无显著差异,而茎密度差异显著.不同冠层高度及生活型间,叶生物量与茎生物量及总生物量之间均呈显著等速生长关系.小枝叶生物量分别与茎直径、茎体积呈显著异速生长关系,且该异速生长指数在不同冠层高度无显著差异.茎长度、茎宽长比及茎密度对当年生小枝叶生物量变异的解释力较小(<24%).冠层高度和生活型对小枝叶-茎生物量的等速分配关系影响不显著.小枝茎构型中,相比于茎长度、茎宽长比以及茎密度,茎的直径与体积对当年生小枝叶生物量的影响更大,冠层高度对当年生小枝茎构型与叶生物量间的异速分配模式无显著影响.     

Stem Cell Glycolipids

Glycolipids are compounds containing one or more monosaccharide residues bound by a glycosidic linkage to a hydrophobic moiety. Because of their expression patterns and the intracellular localization patterns, glycolipids, including stage-specific embryonic antigens (SSEA-3, SSEA-4, and possibly SSEA-1) and gangliosides (e.g., GD3, GD2, and A2B5 antigens), have been used as marker molecules of stem cells. In this review, I will introduce glycolipids expressed in pluripotent stem cells (embryonic stem cells, induced pluripotent stem cells, very small embryonic-like stem cells, amniotic stem cells, and multilineage-differentiating stress enduring cells), multipotent stem cells (neural stem cells, mesenchymal stem cells, fetal liver multipotent progenitor cells, and hematopoietic stem cells), and cancer stem cells (brain cancer stem cells and breast cancer stem cells), and discuss their availability as biomarkers for identifying and isolating stem cells.     

主要干性基因与衰老相关基因表达水平的相互拮抗关系

目前广泛地利用传统的体细胞衰老理论和方法对成体干细胞衰老进行研究,忽视了成体干细胞特有的自我更新功能和相应的干性基因的作用.干性基因的下调可能是导致间充质干细胞衰老的主要原因.通过查阅相关资料发现主要干性基因与衰老相关基因表达水平的相互拮抗关系,这体现在以下4个方面:a.干细胞衰老伴随着干性基因的下调;b.干性基因表达抑制细胞的衰老;c.干性基因抑制衰老相关基因的表达;d.抑制衰老相关基因促进干性基因的表达.干性基因与衰老相关基因的表达水平存在相互拮抗关系,这为成体干细胞衰老可能源于成体干细胞的干性降低的观点提供了坚实的分子基础.     

Numerical simulation of the insertion process of an uncemented hip prosthesis in order to evaluate the influence of residual stress and contact distribution on the stem initial stability

The long-term success of a cementless total hip arthroplasty depends on the implant geometry and interface bonding characteristics (fit, coating and ingrowth) and on stem stiffness. This study evaluates the influence of stem geometry and fitting conditions on the evolution and distribution of the bone–stem contact, stress and strain during and after the hip stem insertion, by means of dynamic finite element techniques. Next, the influence of the mechanical state (bone–stem contact, stress and strain) resulted from the insertion process on the stem initial resistance to subsidence is investigated. In addition, a study on the influence of bone–stem interface conditions (friction) on the insertion process and on the initial stem stability under physiological loading is performed. The results indicate that for a stem with tapered shape the contact in the proximal part of the stem was improved, but contact in the calcar region was achieved only when extra press-fit conditions were considered. Changes in stem geometry towards a more tapered shape and extra press fit and variation in the bone–stem interface conditions (contact amount and high friction) led to a raise in the total insertion force. A direct positive relationship was found between the stem resistance to subsidence and stem geometry (tapering and press fit), bone–stem interface conditions (bone–stem contact and friction interface) and the mechanical status at the end of the insertion (residual stress and strain). Therefore, further studies on evaluating the initial performance of different stem types should consider the parameters describing the bone–stem interface conditions and the mechanical state resulted from the insertion process.     

Epigenetic regulation in adult stem cells and cancers

Adult stem cells maintain tissue homeostasis by their ability to both self-renew and differentiate to distinct cell types. Multiple signaling pathways have been shown to play essential roles as extrinsic cues in maintaining adult stem cell identity and activity. Recent studies also show dynamic regulation by epigenetic mechanisms as intrinsic factors in multiple adult stem cell lineages. Emerging evidence demonstrates intimate crosstalk between these two mechanisms. Misregulation of adult stem cell activity could lead to tumorigenesis, and it has been proposed that cancer stem cells may be responsible for tumor growth and metastasis. However, it is unclear whether cancer stem cells share commonalities with normal adult stem cells. In this review, we will focus on recent discoveries of epigenetic regulation in multiple adult stem cell lineages. We will also discuss how epigenetic mechanisms regulate cancer stem cell activity and probe the common and different features between cancer stem cells and normal adult stem cells.     

青藏高原东南缘陇蜀杜鹃当年生小枝茎叶性状对海拔变化的响应

通过在青藏高原东南缘的岷江源区三处高山林草交错带采集陇蜀杜鹃当年生小枝,测量小枝的茎长、茎粗与茎生物量,沿海拔梯度自然分布的空间变化对比其当年生小枝的茎结构与生物量及其相互关系,接着比较了总叶质量和比叶面积的变化,最后通过典范对应分析(CCA)探究小枝茎叶性状与土壤因子的相关关系,有助于理解陇蜀杜鹃适应异质环境的生态适应对策。结果表明:(1)除弓杠岭外,斗鸡台与卡卡山土壤因子在海拔间差异显著,相似海拔不同山地间土壤因子也存在显著差异。(2)除卡卡山高海拔比叶面积显著小于低海拔外,其他样地的小枝茎性状(茎长、茎粗、比茎长和茎生物量)和叶性状(总叶质量和比叶面积)在海拔间并无显著差异,相似海拔不同坡体间茎粗、茎生物量以及比茎长差异也未达到显著水平(P>0.05),但弓杠岭(3963 m)的茎长显著大于卡卡山(3921 m)(P<0.05)。(3)小枝茎长、茎粗与茎生物量之间均为异速生长关系,且茎生物量累积速率大于茎长和茎粗增加的速率,且茎长的增加速率约为茎粗的2.8倍。(4)CCA排序结果表明,11个土壤环境因子中,碳含量、碳氮比、有机碳含量、总磷和容重对植物性状有显著的影响,但在海拔及不同山体间影响小枝茎叶性状的土壤因子不同。由此可知,较小的海拔梯度变化对小枝茎叶性状影响较小,土壤因子是导致小枝茎叶性状差异的重要原因之一。     

猕猴神经干细胞的诱导分化、干性维持及同种脑内移植

为探索猕猴神经干细胞分化及特性维持,推进神经干细胞临床应用研究,该实验以绿色荧光蛋白(green fluorescence protein,GFP)为标记探讨猕猴胚胎干细胞向玫瑰花环(rosettes)结构神经干细胞的分化及其碱性成纤维细胞生长因子(basic fibroblast growth factor,bFGF)和表皮生长因子(epidermal growth factor,EGF)的扩增培养。结果表明:1)建立了稳定高效的猕猴神经干细胞分化体系,在该分化体系下,GFP标记猕猴胚胎干细胞在分化的第12天时,95%以上的细胞分化为神经干细胞;2)分化得到的Rosettes结构神经干细胞经bFGF/EGF扩增后,能够较好地维持其Rosettes结构;3)经bFGF/EGF扩增后的rosettes结构神经干细胞移植到猕猴脑内后能够较好的存活并向神经元分化,即bFGF/EGF扩增培养能较好地维持Rosettes结构的神经干细胞,且移植到猕猴脑内的该细胞亦能够较好地存活并向神经元分化,该结果为神经干细胞应用于临床提供了基础理论依据。     

帕金森病的细胞治疗研究进展

干细胞为治疗帕金森病提供了新的希望.目前用于研究的干细胞主要有神经干细胞、胚胎干细胞、诱导多功能干细胞、间充质干细胞等.本文回顾了上述细胞在移植治疗帕金森病研究中的进展,并介绍了近期出现的将体细胞直接重编程为神经细胞或神经干细胞的新技术.     

Two different evolutionary origins of stem cell systems and their molecular basis

We propose two major evolutionary origins of stem cell systems in the animal kingdom. Adult pluripotent stem cell systems are found in many invertebrates and probably evolved as components of asexual reproduction. Lineage-specific stem cell systems probably evolved later and include neural and hematopoietic stem cell types. We propose that these two types of stem cell systems evolved independently. The vasa-like genes regulate reproductive stem cells, but not lineage-specific stem cells, which may be regulated by gcm genes. Here, we review the evidence for the molecular basis for the evolutionary origin of these two different stem cell systems.     

干细胞与再生医学研究进展

干细胞具有分化成为体内所有类型细胞的能力,因此,其在再生医学治疗、体外疾病模拟、药物筛选等方面具有广阔的应用前景。干细胞技术在近些年取得了突飞猛进的发展,特别是诱导多能性干细胞的出现使干细胞领域经历了一场巨大的变革。我国干细胞研究在这场干细胞技术变革中取得了多项重大成果,逐渐成为了世界干细胞研究领域中的重要力量。本综述着重介绍近几年来,主要是诱导多能性干细胞技术出现之后,我国在干细胞和再生医学领域取得的重要进展,主要涵盖诱导多能性干细胞、转分化、单倍体干细胞以及基因修饰动物模型和基因治疗等方面。     

The Problem of Stem Cells in Plants

The uppermost cells of the root and shoot apical meristems are considered as stem cells. They are similar, in many features, to the stem cells of animals. But, unlike animals, the stem cells can repeatedly arise in plants during morphogenesis and regeneration or in tissue culture from actively dividing or differentiated cells. When the stem cells are removed, they can be repeatedly restored from the actively dividing cells. The maintenance of the population of stem cells is determined by interaction between the stem cells and actively dividing cells located below according to the feedback principle. The protein synthesized in the stem cells determines how the lower located cells affect the stem cells. Specificity of stem cell identification in plants is discussed.     

The problem of stem cells in plants

The uppermost cells of the root and shoot apical meristems are considered as stem cells. They are similar, in many features, to the stem cells of animals. But, unlike animals, the stem cells can repeatedly arise in plants during morphogenesis and regeneration or in tissue culture from actively dividing or differentiated cells. When the stem cells are removed, they can be repeatedly restored from the actively dividing cells. The maintenance of the population of stem cells is determined by interaction between the stem cells and actively dividing cells located below according to the feedback principle. The protein synthesized in the stem cells determines how the lower located cells affect the stem cells. Specificity of stem cell identification in plants is discussed.     

Stem cell niches

The nature of the stem cell niche and its interaction with stem cells is one of fundamental problems in the biology of stem cells. Stem cell niches are formed during ontogeny. A niche can remain vacant and exist independently of stem cells; however, stem cell self-renewal cannot be maintained for long periods outside of the niche except for particular conditions, e.g., in vitro. A vacant niche can be occupied by excessive or transplanted stem cells and can provide for their functioning. A niche size allows a definite number of stem cells to be maintained. Excessive stem cells either differentiate in the presence of specific signal(s) or undergo apoptosis in the absence of such signal. Thus, the niches control the number of stem cells in the body and protect it from excessive stem cell proliferation. Under particular conditions, stem cells can leave and return to their niches. Stem cells are retained in the niche by cell-to-cell interactions and adhesion to the extracellular matrix. Both the niches and stem cells arise at a particular ontogenetic stage and are capable of long self-renewal. The development can be described in terms of the formation of stem cells and their niches.     

肿瘤干细胞及其耐药机制

肿瘤干细胞是存在于造血系统肿瘤和一些实体瘤中具有干细胞特性的细胞。肿瘤干细胞假说认为,经药物治疗后肿瘤复发和转移与肿瘤干细胞残存有密切关系。其原因可能是肿瘤干细胞高表达ABC转运蛋白和Bcl-2抗凋亡蛋白,同时其本身又具有一些干细胞特性。对肿瘤干细胞耐药机制的研究,将有助于发现新的肿瘤治疗靶点和更好的抗癌策略。     

大兴安岭兴安落叶松(Larix gmelinii)天然林分级木转换特征

通过调查样地,作树干解析,分析了不同结构兴安落叶松天然林分级木（优势木、平均木和被压木）转换特征。研究表明：（1）不同结构的兴安落叶松天然林分级木转换年龄、方向和转换率均不同。兴安落叶松分级木转换率29.4%。分级木中,优势木、平均木和被压木转换率分别35.3%、41.2%、11.8%。分级木转换中,优势木与平均木相互转换比例较高,优势木转平均木占83.3%,平均木转优势木占85.7%;优势木向被压木转换比例仅为16.7%;被压木不能转换成优势木,只能转换成平均木,被压木中无转换占88.2%,在森林经营和抚育采伐中应考虑伐除这些被压木。（2）在林分年龄36～65a范围内,随着林分年龄增大,其转换率呈增加趋势。林分年龄30～39a、50～59a和60～69a时,其转换率分别0、33.3%和46.7%。（3）随着林分密度增加,分级木转换率呈增高趋势。当林分密度小于2500株.hm^-2时,主要于优势木与平均木间转换。当林分密度大于2500株.hm^-2时,才出现其它分级木与被压木相互转换现象。（4）不同林型分级木转换率和转换方向不同。草类-落叶松和杜香-落叶松林分级木转换率分别50%和9.5%。（5）不同水平格局林分分级木转换率不同。聚集分布和随机分布时,其转换率分别61.1%和13.3%。     

Application of dental stem cells in three-dimensional tissue regeneration

Dental stem cells can differentiate into different types of cells. Dental pulp stem cells, stem cells from human exfoliated deciduous teeth, periodontal ligament stem cells, stem cells from apical papilla, and dental follicle progenitor cells are five different types of dental stem cells that have been identified during different stages of tooth development. The availability of dental stem cells from discarded or removed teeth makes them promising candidates for tissue engineering. In recent years, three-dimensional (3D) tissue scaffolds have been used to reconstruct and restore different anatomical defects. With rapid advances in 3D tissue engineering, dental stem cells have been used in the regeneration of 3D engineered tissue. This review presents an overview of different types of dental stem cells used in 3D tissue regeneration, which are currently the most common type of stem cells used to treat human tissue conditions.