世界生命科学前沿动态周报（四十七）

【点评】
    能够彻底纯化人体造血干细胞无论是对干细胞的基础研究还是对干细胞临床应用开发都是一个突破性进展。这一发现最终准确定位了整个血液系统的发源地。

【参考论文Science, 2011; 333 (6039): 218 DOI:10.1126/science.1201219
Isolation of Single Human Hematopoietic Stem Cells Capable of Long-Term Multilineage Engraftment
F. Notta, S. Doulatov, E. Laurenti, et al.
Lifelong blood cell production is dependent on rare hematopoietic stem cells (HSCs) to perpetually replenish mature cells via a series of lineage-restricted intermediates. Investigating the molecular state of HSCs is contingent on the ability to purify HSCs away from transiently engrafting cells. We demonstrated that human HSCs remain infrequent, using current purification strategies based on Thy1 (CD90) expression. By tracking the expression of several adhesion molecules in HSC-enriched subsets, we revealed CD49f as a specific HSC marker. Single CD49f+ cells were highly efficient in generating long-term multilineage grafts, and the loss of CD49f expression identified transiently engrafting multipotent progenitors (MPPs). The demarcation of human HSCs and MPPs will enable the investigation of the molecular determinants of HSCs, with a goal of developing stem cell–based therapeutics.

3. 乙酰辅酶A水平影响细胞生长增殖
【动态】
　　美国科学家最近发现乙酰辅酶A通过促进生长基因上的组蛋白乙酰化来诱导细胞生长和增殖。细胞进入生长和分化的决定必须与其可用营养和代谢状态密切配合。这些代谢和营养方面的要求条件及其诱导细胞生长增殖的机理还很不清楚。美国科学家报道了乙酰辅酶A作为碳源的下游代谢产物代表了一种有关生长增殖的关键代谢信号。在进入生长周期时，细胞内乙酰辅酶A的水平有实质性增长结果诱导重要的生长基因上的组蛋白进行Gcn5p/SAGA 催化的乙酰化，由此促使他们能够快速转录并致力于细胞生长。 因此，乙酰辅酶A起到碳源“变阻器”的作用，通过促进生长基因上的特殊组蛋白的乙酰化来启动细胞生长程序。

【点评】
　 细胞内乙酰辅酶A的水平影响生长基因上的组蛋白的乙酰化水平，进而影响细胞进入生长和分化的决定。营养和代谢状态决定着细胞生长和增殖，乙酰辅酶A作为关键代谢信号起重要作用。

【参考论文】Molecular Cell, 2011 42(4): 426-437
Acetyl-CoA Induces Cell Growth and Proliferation by Promoting the Acetylation of Histones at Growth Genes
Ling Cai, Benjamin M. Sutter, Bing Li, and Benjamin P. Tu
The decision by a cell to enter a round of growth and division must be intimately coordinated with nutrient availability and its metabolic state. These metabolic and nutritional requirements, and the mechanisms by which they induce cell growth and proliferation, remain poorly understood. Herein, we report that acetyl-CoA is the downstream metabolite of carbon sources that represents a critical metabolic signal for growth and proliferation. Upon entry into growth, intracellular acetyl-CoA levels increase substantially and consequently induce the Gcn5p/SAGA-catalyzed acetylation of histones at genes important for growth, thereby enabling their rapid transcription and commitment to growth. Thus, acetyl-CoA functions as a carbon-source rheostat that signals the initiation of the cellular growth program by promoting the acetylation of histones specifically at growth genes.

4. 卵巢上皮细胞癌变过程中生物力学特征的变化
【动态】  
    癌细胞侵袭性的表现被认为是除遗传变化外，还与生物力学和细胞骨架结构的改变有关。美国科学家的一项最新研究测定了老鼠卵巢表面上皮细胞癌变过程中细胞的粘弹性的变化，发现在它们还是良性的时候更硬更粘，细胞变形性的增加直接与癌变进程相关。细胞骨架结构中肌动蛋白水平的下降直接与细胞生物力学性质的变化相关。不同癌症阶段的不同生物力学表现有助于癌症的诊断、风险评估和提高治疗效果。该研究中，癌变细胞相比未癌变的健康细胞，显得更软和变形更快，流动性也增加了。

【点评】
    细胞生物力学性质的变化揭示了癌症的发展阶段，将生物学问题的物理学特征呈现出来。开阔了癌症研究乃至生物学研究的视野，也有助于从新的角度研究和解决癌症难题。

【参考论文】Nanomedicine: Nanotechnology, Biology and Medicine, 2011; doi: 10.1016/j.nano.2011.05.012
The effects of cancer progression on the viscoelasticity of ovarian cell cytoskeleton structures
Alperen N. Ketene, Eva M. Schmelz, Paul C. Roberts, Masoud Agah
Alterations in the biomechanical properties and cytoskeletal organization of cancer cells in addition to genetic changes have been correlated with their aggressive phenotype. In this study, we investigated changes in the viscoelasticity of mouse ovarian surface epithelial (MOSE) cells, a mouse model for progressive ovarian cancer. We demonstrate that the elasticity of late-stage MOSE cells (0.549 ± 0.281 kPa) were significantly less than that of their early-stage counterparts (1.097 ± 0.632 kPa). Apparent cell viscosity also decreased significantly from early (144.7 ± 102.4 Pa-s) to late stage (50.74 ± 29.72 Pa-s). This indicates that ovarian cells are stiffer and more viscous when they are benign. The increase in cell deformability directly correlates with the progression of a transformed phenotype from a nontumorigenic, benign cell to a tumorigenic, malignant one. The decrease in the level of actin in the cytoskeleton and its organization is directly associated with the changes in cell biomechanical property.

5. 中枢神经系统损伤后形成的疤痕来源于周细胞
【动态】
    瑞典科学家在最近的科学杂志上报道了他们发现了中枢神经损伤后形成疤痕组织的细胞来源是周细胞。中枢神经损伤后缺损组织的再生能力很有限，损伤会被疤痕组织封闭。由于此疤痕组织富含星形胶质细胞，常被认为是神经胶质疤痕，其作用复杂，被探讨了一个多世纪了。该研究发现在受伤脊髓中形成疤痕的基质细胞是由一种特殊亚型的周细胞派生来的，在伤处该周细胞数目多于星形胶质细胞。阻断该细胞的繁衍会使受伤组织无法闭合。该发现提供了一种组织纤维化的细胞来源。

【点评】
    中枢神经损伤后形成的疤痕组织来源于周细胞的发现，有助于促进神经损伤修复的研究。

【参考论文】Science 8 July 2011: Vol. 333 no. 6039 pp. 238-242，DOI: 10.1126/science.1203165
A Pericyte Origin of Spinal Cord Scar Tissue
Christian Göritz, David O. Dias, Nikolay Tomilin, et al.
There is limited regeneration of lost tissue after central nervous system injury, and the lesion is sealed with a scar. The role of the scar, which often is referred to as the glial scar because of its abundance of astrocytes, is complex and has been discussed for more than a century. Here we show that a specific pericyte subtype gives rise to scar-forming stromal cells, which outnumber astrocytes, in the injured spinal cord. Blocking the generation of progeny by this pericyte subtype results in failure to seal the injured tissue. The formation of connective tissue is common to many injuries and pathologies, and here we demonstrate a cellular origin of fibrosis.

6. 间充质干细胞--体内的创伤药房
【动态】
    研究表明体内间充质干细胞位于血管周，只关注它们多向分化能力的传统观点也该扩展到包含那些拓宽其治疗前景的同样吸引人的功能如细胞调节。细胞杂志的一篇综述就此问题的已有证据进行了研究，结果发现在局部损伤中，间充质干细胞从血管周的位置释放出来，激活，通过分泌生物活性分子和调节局部免疫反应建立再生的微环境。这些营养和免疫调节行为显示间充质干细胞可能充当了体内管理损伤部位的“药房”。这一能够形成多种不同组织的干细胞在起自然保护、治疗和生产抗生素的作用。

【点评】
    间充质干细胞越来越多的重要作用被揭示出来，充分说明该种干细胞在体内的重要意义，如何体内营造适于它生活的环境应该成为发挥其生理功能的重要研究课题。