Efficient transplantation via antibody-based clearance of hematopoietic stem cell niches

Upon intravenous transplantation, hematopoietic stem cells (HSCs) can home to specialized niches, yet most HSCs fail to engraft unless recipients are subjected to toxic preconditioning. We provide evidence that, aside from immune barriers, donor HSC engraftment is restricted by occupancy of appropriate niches by host HSCs. Administration of ACK2, an antibody that blocks c-kit function, led to the transient removal of >98% of endogenous HSCs in immunodeficient mice. Subsequent transplantation of these mice with donor HSCs led to chimerism levels of up to 90%. Extrapolation of these methods to humans may enable mild but effective conditioning regimens for transplantation.     

Out of Eden: stem cells and their niches

Stem cells are currently in the news for two reasons: the successful cultivation of human embryonic stem cell lines and reports that adult stem cells can differentiate into developmentally unrelated cell types, such as nerve cells into blood cells. Both intrinsic and extrinsic signals regulate stem cell fate and some of these signals have now been identified. Certain aspects of the stem cell microenvironment, or niche, are conserved between tissues, and this can be exploited in the application of stem cells to tissue replacement therapy.     

Germline stem cells anchored by adherens junctions in the Drosophila ovary niches

How stem cells are recruited to and maintained in their niches is crucial to understanding their regulation and use in regenerative medicine. Here, we demonstrate that DE-cadherin-mediated cell adhesion is required for anchoring germline stem cells (GSCs) in their niches in the Drosophila ovary. Two major components of this adhesion process, DE-cadherin and Armadillo/beta-catenin, accumulate at high levels in the junctions between GSCs and cap cells, one of the niche components. Removal of these proteins from GSCs results in stem cell loss. Furthermore, DE-cadherin is required for recruiting GSCs to their niche. Our study demonstrates that anchorage of GSCs in their niche by DE-cadherin-mediated adhesion is important for stem cell maintenance and function.     

Lineage tracing reveals Lgr5+ stem cell activity in mouse intestinal adenomas

The concept that tumors are maintained by dedicated stem cells, the so-called cancer stem cell hypothesis, has attracted great interest but remains controversial. Studying mouse models, we provide direct, functional evidence for the presence of stem cell activity within primary intestinal adenomas, a precursor to intestinal cancer. By "lineage retracing" using the multicolor Cre-reporter R26R-Confetti, we demonstrate that the crypt stem cell marker Lgr5 (leucine-rich repeat-containing heterotrimeric guanine nucleotide-binding protein-coupled receptor 5) also marks a subpopulation of adenoma cells that fuel the growth of established intestinal adenomas. These Lgr5(+) cells, which represent about 5 to 10% of the cells in the adenomas, generate additional Lgr5(+) cells as well as all other adenoma cell types. The Lgr5(+) cells are intermingled with Paneth cells near the adenoma base, a pattern reminiscent of the architecture of the normal crypt niche.     

Fetal and adult hematopoietic stem cells give rise to distinct T cell lineages in humans

Although the mammalian immune system is generally thought to develop in a linear fashion, findings in avian and murine species argue instead for the developmentally ordered appearance (or "layering") of distinct hematopoietic stem cells (HSCs) that give rise to distinct lymphocyte lineages at different stages of development. Here we provide evidence of an analogous layered immune system in humans. Our results suggest that fetal and adult T cells are distinct populations that arise from different populations of HSCs that are present at different stages of development. We also provide evidence that the fetal T cell lineage is biased toward immune tolerance. These observations offer a mechanistic explanation for the tolerogenic properties of the developing fetus and for variable degrees of immune responsiveness at birth.     

突脉青冈群落乔木层优势种群生态位研究

采用统计学、数学方法对突脉青冈群落乔木层生态位状况进行定量分析,揭示突脉青冈群落优势种群生态位特征,以恢复其退化生态系统的树种结构和生态功能。结果表明,突脉青冈和米槠生态位较宽,其生态位值分别为0.96和0.83,群落内其它树种的生态位宽度在0.2-0.4之间。生态位相似比例和生态位重叠值表明生态位宽度较大的种,在群落中与其他种生态位相似比例和生态位重叠值较高。说明突脉青冈和米槠2个树种是群落中的优势种群,能更好地适应当地环境,充分利用群落中的资源。该群落继续向前发展,可能发展成为突脉青冈和米槠占优势的顶级群落。     

Multipotent Drosophila intestinal stem cells specify daughter cell fates by differential notch signaling

The adult Drosophila midgut contains multipotent intestinal stem cells (ISCs) scattered along its basement membrane that have been shown by lineage analysis to generate both enterocytes and enteroendocrine cells. ISCs containing high levels of cytoplasmic Delta-rich vesicles activate the canonical Notch pathway and down-regulate Delta within their daughters, a process that programs these daughters to become enterocytes. ISCs that express little vesiculate Delta, or are genetically impaired in Notch signaling, specify their daughters to become enteroendocrine cells. Thus, ISCs control daughter cell fate by modulating Notch signaling over time. Our studies suggest that ISCs actively coordinate cell production with local tissue requirements by this mechanism.     

Theta-bearing and complement-receptor lymphocytes are distinct populations of cells

In the mouse, most (or all) complement-receptor lymphocytes and theta-bearing lymphocytes are part of nonoverlapping populations of cells. This finding validates the use of these membrane markers to characterize populations of lymphocytes. In addition, it is probable that, although receptors for complement and membrane-bound immunoglobulins coexist on the same lymphoid cells, these markers are located at separate sites on the membrane.     

Vasopressin and oxytocin excite distinct neuronal populations in the central amygdala

Vasopressin and oxytocin strongly modulate autonomic fear responses, through mechanisms that are still unclear. We describe how these neuropeptides excite distinct neuronal populations in the central amygdala, which provides the major output of the amygdaloid complex to the autonomic nervous system. We identified these two neuronal populations as part of an inhibitory network, through which vasopressin and oxytocin modulate the integration of excitatory information from the basolateral amygdala and cerebral cortex in opposite manners. Through this network, the expression and endogenous activation of vasopressin and oxytocin receptors may regulate the autonomic expression of fear.     

凤阳山红豆杉群落乔木层主要种群生态位研究

红豆杉为我国特有的国家一级保护植物.通过Shannon-wiener生态位计测公式和对称α法(Pianka公式)对凤阳山红豆杉群落的样方调查数据进行分析,研究了凤阳山红豆杉所在群落主要种群的种间关系及其群落特征.结果表明:凤阳山红豆杉群落大致可分成两个群落类型:福建柏-猴头杜鹃林(群落Ⅰ)和褐叶青冈-木荷-甜槠林(群落Ⅱ),其中群落Ⅰ较适合红豆杉生长与更新;红豆杉在群落Ⅰ和群落Ⅱ中的生态位宽度值分别为0.248、0.337.在所属群落类型中分别排在第10位与第7位,其在群落Ⅱ中对资源的利用率较高;红豆杉在群落Ⅱ与其它物种的生态位重叠值大于群落Ⅰ,说明红豆杉在群落Ⅱ中的潜在竞争较大.推测当资源不足时,红豆杉在群落Ⅱ中极易与其它物种发生资源竞争.总体现之,在凤阳山自然保护区内红豆杉的保护应以生境保护和培育为主,建议将群落类型Ⅰ作为重点保护类型.     

Two distinct populations of calcium channels in a clonal line of pituitary cells

The whole-cell variant of the patch clamp technique was used to study calcium channels in GH3 cells. Two distinct populations of calcium channels, first recognized from their closing kinetics, were observed. The slowly closing channels are activated in a relatively negative voltage range and are inactivated within 100 milliseconds. They conduct barium and calcium about equally well. The fast closing channels are activated at more positive voltages, are not inactivated during a 100-millisecond pulse, conduct barium in preference to calcium, and are activated slightly more rapidly than the slowly closing channels.     

Wolbachia enhance Drosophila stem cell proliferation and target the germline stem cell niche

Wolbachia are widespread maternally transmitted intracellular bacteria that infect most insect species and are able to alter the reproduction of innumerous hosts. The cellular bases of these alterations remain largely unknown. Here, we report that Drosophila mauritiana infected with a native Wolbachia wMau strain produces about four times more eggs than the noninfected counterpart. Wolbachia infection leads to an increase in the mitotic activity of germline stem cells (GSCs), as well as a decrease in programmed cell death in the germarium. Our results suggest that up-regulation of GSC division is mediated by a tropism of Wolbachia for the GSC niche, the cellular microenvironment that supports GSCs.     

A stem cell molecular signature

Mechanisms regulating self-renewal and cell fate decisions in mammalian stem cells are poorly understood. We determined global gene expression profiles for mouse and human hematopoietic stem cells and other stages of the hematopoietic hierarchy. Murine and human hematopoietic stem cells share a number of expressed gene products, which define key conserved regulatory pathways in this developmental system. Moreover, in the mouse, a portion of the genetic program of hematopoietic stem cells is shared with embryonic and neural stem cells. This overlapping set of gene products represents a molecular signature of stem cells.     

Fluctuation tests with antibody-forming spleen cell populations

Shortly after immunization of mice, cells forming specific antibodies to one antigen, for example, sheep red blood cells, are nonrandomly distributed throughout the spleen. If the spleen donor has been immunized with two different antigens, for example, sheep red blood cells and chicken red blood cells, the nonrandom distribution of spleen cells forming antibody to one antigen differs significantly from that of cells forming antibody to the other antigen. These findings are in accord with a clonal distribution of antibody-forming cells.