世界生命科學(xué)前沿動態(tài)周報（四十七）

【點評】
    能夠徹底純化人體造血干細胞無論是對干細胞的基礎(chǔ)研究還是對干細胞臨床應(yīng)用開發(fā)都是一個突破性進展。這一發(fā)現(xiàn)最終準確定位了整個血液系統(tǒng)的發(fā)源地。

【參考論文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. 乙酰輔酶A水平影響細胞生長增殖
【動態(tài)】
　　美國科學(xué)家最近發(fā)現(xiàn)乙酰輔酶A通過促進生長基因上的組蛋白乙?；瘉碚T導(dǎo)細胞生長和增殖。細胞進入生長和分化的決定必須與其可用營養(yǎng)和代謝狀態(tài)密切配合。這些代謝和營養(yǎng)方面的要求條件及其誘導(dǎo)細胞生長增殖的機理還很不清楚。美國科學(xué)家報道了乙酰輔酶A作為碳源的下游代謝產(chǎn)物代表了一種有關(guān)生長增殖的關(guān)鍵代謝信號。在進入生長周期時，細胞內(nèi)乙酰輔酶A的水平有實質(zhì)性增長結(jié)果誘導(dǎo)重要的生長基因上的組蛋白進行Gcn5p/SAGA 催化的乙酰化，由此促使他們能夠快速轉(zhuǎn)錄并致力于細胞生長。 因此，乙酰輔酶A起到碳源“變阻器”的作用，通過促進生長基因上的特殊組蛋白的乙?；瘉韱蛹毎L程序。

【點評】
　 細胞內(nèi)乙酰輔酶A的水平影響生長基因上的組蛋白的乙?；?，進而影響細胞進入生長和分化的決定。營養(yǎng)和代謝狀態(tài)決定著細胞生長和增殖，乙酰輔酶A作為關(guān)鍵代謝信號起重要作用。

【參考論文】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. 卵巢上皮細胞癌變過程中生物力學(xué)特征的變化
【動態(tài)】  
    癌細胞侵襲性的表現(xiàn)被認為是除遺傳變化外，還與生物力學(xué)和細胞骨架結(jié)構(gòu)的改變有關(guān)。美國科學(xué)家的一項最新研究測定了老鼠卵巢表面上皮細胞癌變過程中細胞的粘彈性的變化，發(fā)現(xiàn)在它們還是良性的時候更硬更粘，細胞變形性的增加直接與癌變進程相關(guān)。細胞骨架結(jié)構(gòu)中肌動蛋白水平的下降直接與細胞生物力學(xué)性質(zhì)的變化相關(guān)。不同癌癥階段的不同生物力學(xué)表現(xiàn)有助于癌癥的診斷、風(fēng)險評估和提高治療效果。該研究中，癌變細胞相比未癌變的健康細胞，顯得更軟和變形更快，流動性也增加了。

【點評】
    細胞生物力學(xué)性質(zhì)的變化揭示了癌癥的發(fā)展階段，將生物學(xué)問題的物理學(xué)特征呈現(xiàn)出來。開闊了癌癥研究乃至生物學(xué)研究的視野，也有助于從新的角度研究和解決癌癥難題。

【參考論文】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. 中樞神經(jīng)系統(tǒng)損傷后形成的疤痕來源于周細胞
【動態(tài)】
    瑞典科學(xué)家在最近的科學(xué)雜志上報道了他們發(fā)現(xiàn)了中樞神經(jīng)損傷后形成疤痕組織的細胞來源是周細胞。中樞神經(jīng)損傷后缺損組織的再生能力很有限，損傷會被疤痕組織封閉。由于此疤痕組織富含星形膠質(zhì)細胞，常被認為是神經(jīng)膠質(zhì)疤痕，其作用復(fù)雜，被探討了一個多世紀了。該研究發(fā)現(xiàn)在受傷脊髓中形成疤痕的基質(zhì)細胞是由一種特殊亞型的周細胞派生來的，在傷處該周細胞數(shù)目多于星形膠質(zhì)細胞。阻斷該細胞的繁衍會使受傷組織無法閉合。該發(fā)現(xiàn)提供了一種組織纖維化的細胞來源。

【點評】
    中樞神經(jīng)損傷后形成的疤痕組織來源于周細胞的發(fā)現(xiàn)，有助于促進神經(jīng)損傷修復(fù)的研究。

【參考論文】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. 間充質(zhì)干細胞--體內(nèi)的創(chuàng)傷藥房
【動態(tài)】
    研究表明體內(nèi)間充質(zhì)干細胞位于血管周，只關(guān)注它們多向分化能力的傳統(tǒng)觀點也該擴展到包含那些拓寬其治療前景的同樣吸引人的功能如細胞調(diào)節(jié)。細胞雜志的一篇綜述就此問題的已有證據(jù)進行了研究，結(jié)果發(fā)現(xiàn)在局部損傷中，間充質(zhì)干細胞從血管周的位置釋放出來，激活，通過分泌生物活性分子和調(diào)節(jié)局部免疫反應(yīng)建立再生的微環(huán)境。這些營養(yǎng)和免疫調(diào)節(jié)行為顯示間充質(zhì)干細胞可能充當(dāng)了體內(nèi)管理損傷部位的“藥房”。這一能夠形成多種不同組織的干細胞在起自然保護、治療和生產(chǎn)抗生素的作用。

【點評】
    間充質(zhì)干細胞越來越多的重要作用被揭示出來，充分說明該種干細胞在體內(nèi)的重要意義，如何體內(nèi)營造適于它生活的環(huán)境應(yīng)該成為發(fā)揮其生理功能的重要研究課題。