世界生命科學(xué)前沿動(dòng)態(tài)周報(bào)（三十七）

（12.20-12.31/2010）
美寶國(guó)際集團(tuán):陶國(guó)新 
---2010再生科學(xué)年度進(jìn)展 

 　　本次動(dòng)態(tài)包括以下內(nèi)容：耐力鍛煉使心肌細(xì)胞增殖的機(jī)理；癌癥干細(xì)胞基因表達(dá)高癌癥治療結(jié)果差；無(wú)需標(biāo)記實(shí)時(shí)觀察活組織中分子運(yùn)動(dòng)；果蠅激活生殖細(xì)胞遺傳基因來(lái)產(chǎn)生腫瘤；癌細(xì)胞自我毀滅與自我保護(hù)的信號(hào)分子；微小RNA表達(dá)模式的整體圖譜區(qū)分干細(xì)胞類別。以及2010各期中出現(xiàn)過(guò)的比較突出的幾項(xiàng)再生科學(xué)進(jìn)展的小結(jié)。

1. 耐力鍛煉使心肌細(xì)胞增殖的機(jī)理
【摘要】
人們都知道鍛煉身體可以促進(jìn)新陳代謝，有益于心血管健康，但此前科學(xué)家對(duì)運(yùn)動(dòng)究竟如何影響心臟卻所知甚少。美國(guó)哈佛大學(xué)醫(yī)學(xué)院的研究人員日前報(bào)告說(shuō)，他們首次從分子水平發(fā)現(xiàn)運(yùn)動(dòng)有益心臟健康的機(jī)理，這一發(fā)現(xiàn)將有助于開(kāi)發(fā)出治療心血管疾病的新療法。研究人員通過(guò)小鼠實(shí)驗(yàn)發(fā)現(xiàn)，經(jīng)常運(yùn)動(dòng)可以使小鼠體內(nèi)的C/EBPβ轉(zhuǎn)錄因子水平顯著下降，其結(jié)果會(huì)促進(jìn)小鼠心臟肌肉細(xì)胞增殖，有益于心臟生長(zhǎng)。此外，研究人員還發(fā)現(xiàn)，體內(nèi)C/EBPβ水平較低的小鼠對(duì)心力衰竭具有抵抗能力。研究人員表示，這項(xiàng)研究對(duì)心臟肌肉再生的潛力有了深入理解。參與研究的哈佛大學(xué)醫(yī)學(xué)院教授安東尼·羅森茨魏希表示，通過(guò)這項(xiàng)研究可以開(kāi)發(fā)出針對(duì)那些無(wú)法運(yùn)動(dòng)的心臟病患者的療法。這項(xiàng)研究成果發(fā)表在新一期美國(guó)《細(xì)胞》雜志上。（來(lái)源：新華社）

【點(diǎn)評(píng)】
　　該研究所發(fā)現(xiàn)的心肌增殖機(jī)理同樣有助于理解非藥物方式實(shí)現(xiàn)組織再生的機(jī)制并促進(jìn)此類自然再生方法的推廣。

【原文摘錄】Cell, Volume 143, Issue 7, 1072-1083, 23 December 2010
C/EBPβ Controls Exercise-Induced Cardiac Growth and Protects against Pathological Cardiac Remodeling
Pontus Boström, Nina Mann, Jun Wu, et al.
The heart has the ability to grow in size in response to exercise, but little is known about the transcriptional mechanisms underlying physiological hypertrophy. Adult cardiomyocytes have also recently been proven to hold the potential for proliferation, a process that could be of great importance for regenerative medicine. Using a unique RT-PCR-based screen against all transcriptional components, we showed that C/EBPβ was downregulated with exercise, whereas the expression of CITED4 was increased. Reduction of C/EBPβ in vitro and in vivo resulted in a phenocopy of endurance exercise with cardiomyocyte hypertrophy and proliferation. This proliferation was mediated, at least in part, by the increased CITED4. Importantly, mice with reduced cardiac C/EBPβ levels displayed substantial resistance to cardiac failure upon pressure overload. These data indicate that C/EBPβ represses cardiomyocyte growth and proliferation in the adult mammalian heart and that reduction in C/EBPβ is a central signal in physiologic hypertrophy and proliferation.

2. 癌癥干細(xì)胞基因表達(dá)高癌癥治療結(jié)果差
【摘要】  
　　據(jù)美國(guó)物理學(xué)家組織網(wǎng)12月22日（北京時(shí)間）報(bào)道，斯坦福大學(xué)研究人員通過(guò)對(duì)白血病干細(xì)胞的基因表達(dá)方式研究發(fā)現(xiàn)，癌癥干細(xì)胞基因表達(dá)水平更高的病人比表達(dá)水平低的病人預(yù)后效果要差很多，該發(fā)現(xiàn)首次通過(guò)臨床數(shù)據(jù)證明了癌癥干細(xì)胞概念。醫(yī)療人員可據(jù)此預(yù)測(cè)群體病人的治療結(jié)果，并幫助開(kāi)發(fā)新的臨床療法。研究發(fā)表在12月22日的《美國(guó)醫(yī)學(xué)會(huì)雜志》（JAMA）上。幾年前提出的癌癥干細(xì)胞概念認(rèn)為，某些癌癥起源于一小撮自我更新能力很強(qiáng)的細(xì)胞，這一小撮細(xì)胞即是癌癥干細(xì)胞。這些癌癥干細(xì)胞能不斷補(bǔ)充生成新的癌癥細(xì)胞，癌癥要徹底治療，必須清除這些干細(xì)胞。癌癥干細(xì)胞對(duì)抗治療已經(jīng)在一些固狀腫瘤和血癌的動(dòng)物模型中得到驗(yàn)證，雖然有大量實(shí)驗(yàn)室證據(jù)支持，但至今還缺乏臨床證據(jù)。論文合著者、斯坦福癌癥中心醫(yī)務(wù)部艾什·埃里沙德和同事拉文達(dá)·馬杰提今年9月曾在實(shí)驗(yàn)室小鼠中，對(duì)非霍奇森淋巴瘤癌癥干細(xì)胞表面發(fā)現(xiàn)的蛋白質(zhì)CD47研究發(fā)現(xiàn)，CD47是癌癥干細(xì)胞的“保護(hù)傘”，有了它，很多藥物對(duì)這些細(xì)胞無(wú)效。CD47在其他幾種癌癥干細(xì)胞中也存在。馬杰提認(rèn)為這些動(dòng)物實(shí)驗(yàn)中發(fā)現(xiàn)的證據(jù)在人體中也應(yīng)該存在。他們用兩種能識(shí)別白血病干細(xì)胞的表面標(biāo)記，從7個(gè)白血病患者的腫瘤樣本中分離出這些白血病干細(xì)胞，將腫瘤干細(xì)胞和其他腫瘤細(xì)胞的基因表達(dá)方式進(jìn)行了對(duì)比，結(jié)果有52%的基因表達(dá)不同。癌癥干細(xì)胞基因表達(dá)方式和正常的血液干細(xì)胞很相似，不僅能自我更新，還能像正常干細(xì)胞在需要時(shí)候才分裂。為了逃避那些針對(duì)迅速分裂細(xì)胞的傳統(tǒng)治療方法，它會(huì)選擇少量分裂，潛伏著，等待機(jī)會(huì)“東山再起”。
　　研究人員還對(duì)來(lái)自1000多位急性骨髓白血病病人的4組腫瘤樣本進(jìn)行了對(duì)比研究，發(fā)現(xiàn)在“癌癥干細(xì)胞基因高表達(dá)”和“治療結(jié)果差”之間存在很強(qiáng)的相關(guān)性。在一組德國(guó)樣本中，高表達(dá)病人3年內(nèi)死亡的絕對(duì)風(fēng)險(xiǎn)高達(dá)78%，而低表達(dá)病人僅為57%。同樣，無(wú)病生存率、某個(gè)時(shí)期再度惡化可能性、對(duì)抗初次治療頑固性等指標(biāo)也如此。論文第一作者、斯坦福大學(xué)癌癥系統(tǒng)生物學(xué)中心安德魯·簡(jiǎn)托斯表示，白血病干細(xì)胞的信號(hào)越強(qiáng)，病人壽命越短，病情惡化得越快，治療效果就更差。目前，研究小組正在繼續(xù)研究數(shù)據(jù)，以最終從各種結(jié)合抗體療法中確定哪些療法對(duì)癌癥干細(xì)胞高表達(dá)基因信號(hào)的病人最有效。（來(lái)源：科技日?qǐng)?bào) 發(fā)布時(shí)間：2010-12-23 10:20:47）

【點(diǎn)評(píng)】
　　該研究發(fā)現(xiàn)了白血病干細(xì)胞基因的高表達(dá)與急性粒細(xì)胞白血病的治療效果差之間有獨(dú)立的相關(guān)性，但是并沒(méi)有證明癌癥干細(xì)胞是腫瘤發(fā)生的起因。

【原文摘錄】 JAMA. 2010;304(24):2706-2715. doi: 10.1001/jama.2010.1862
Association of a Leukemic Stem Cell Gene Expression Signature With Clinical Outcomes in Acute Myeloid Leukemia
Andrew J. Gentles, Sylvia K. Plevritis, Ravindra Majeti, Ash A. Alizadeh
Abstract
Context In many cancers, specific subpopulations of cells appear to be uniquely capable of initiating and maintaining tumors. The strongest support for this cancer stem cell model comes from transplantation assays in immunodeficient mice, which indicate that human acute myeloid leukemia (AML) is driven by self-renewing leukemic stem cells (LSCs). This model has significant implications for the development of novel therapies, but its clinical relevance has yet to be determined.
Objective To identify an LSC gene expression signature and test its association with clinical outcomes in AML.
Design, Setting, and Patients Retrospective study of global gene expression (microarray) profiles of LSC-enriched subpopulations from primary AML and normal patient samples, which were obtained at a US medical center between April 2005 and July 2007, and validation data sets of global transcriptional profiles of AML tumors from 4 independent cohorts (n = 1047).
Main Outcome Measures Identification of genes discriminating LSC-enriched populations from other subpopulations in AML tumors; and association of LSC-specific genes with overall, event-free, and relapse-free survival and with therapeutic response.
Results Expression levels of 52 genes distinguished LSC-enriched populations from other subpopulations in cell-sorted AML samples. An LSC score summarizing expression of these genes in bulk primary AML tumor samples was associated with clinical outcomes in the 4 independent patient cohorts. High LSC scores were associated with worse overall, event-free, and relapse-free survival among patients with either normal karyotypes or chromosomal abnormalities. For the largest cohort of patients with normal karyotypes (n = 163), the LSC score was significantly associated with overall survival as a continuous variable (hazard ratio [HR], 1.15; 95% confidence interval [CI], 1.08-1.22; log-likelihood P <.001). The absolute risk of death by 3 years was 57% (95% CI, 43%-67%) for the low LSC score group compared with 78% (95% CI, 66%-86%) for the high LSC score group (HR, 1.9 [95% CI, 1.3-2.7]; log-rank P = .002). In another cohort with available data on event-free survival for 70 patients with normal karyotypes, the risk of an event by 3 years was 48% (95% CI, 27%-63%) in the low LSC score group vs 81% (95% CI, 60%-91% ) in the high LSC score group (HR, 2.4 [95% CI, 1.3-4.5]; log-rank P = .006). In multivariate Cox regression including age, mutations in FLT3 and NPM1, and cytogenetic abnormalities, the HRs for LSC score in the 3 cohorts with data on all variables were 1.07 (95% CI, 1.01-1.13; P = .02), 1.10 (95% CI, 1.03-1.17; P = .005), and 1.17 (95% CI, 1.05-1.30; P = .005).
Conclusion High expression of an LSC gene signature is independently associated with adverse outcomes in patients with AML.

3. 無(wú)需標(biāo)記實(shí)時(shí)觀察活組織中分子運(yùn)動(dòng)
【摘要】  
　　美國(guó)哈佛大學(xué)科學(xué)家將受激拉曼散射（SRS）顯微鏡和核磁共振成像（MRI）技術(shù)結(jié)合，研制出一種最新的生物醫(yī)學(xué)成像設(shè)備，極大拓展了SRS顯微鏡的視野。其速度之快精度之高，如同“視頻”，足以使科學(xué)家直接目睹分子在活組織中的運(yùn)動(dòng)。研究論文發(fā)表在最新一期《科學(xué)》雜志上?！按饲埃琒RS顯微鏡每分鐘只能拍攝一幅畫面，用于活的動(dòng)物或人體就太慢了?！惫鸫髮W(xué)化學(xué)與化學(xué)生物學(xué)教授謝曉亮說(shuō)，“我們大大提高了采集數(shù)據(jù)的速度，使拍攝達(dá)到了視頻速率?！毖芯啃〗M還用這種新型SRS顯微鏡追蹤藥物在皮膚下的移動(dòng)，其能清晰顯示出藥物實(shí)時(shí)吸收情況。如與內(nèi)鏡檢查術(shù)結(jié)合，還能一層一層觀察組織的三維結(jié)構(gòu)。新型SRS顯微鏡的工作原理是探測(cè)原子之間化學(xué)鍵的內(nèi)在震動(dòng)，由于融合了MRI技術(shù)，在透視深度上更適合拍攝體內(nèi)器官和其他大目標(biāo)，既可廣泛用于拍攝器官和組織結(jié)構(gòu)的靜態(tài)圖像，也能在亞細(xì)胞水平以流動(dòng)畫面觀察細(xì)胞中的蛋白質(zhì)、脂質(zhì)和水。
　　同多種常用的觀察生物分子的技術(shù)相比，新型SRS顯微鏡優(yōu)勢(shì)明顯。它能采集分析照射生物樣本的近30%激光，比傳統(tǒng)SRS顯微鏡高出30倍；并且不需要插入熒光標(biāo)記，避免了綠色熒光標(biāo)記蛋白質(zhì)擾亂生物路徑或壓住較小生物分子的問(wèn)題。此外，傳統(tǒng)的紅外顯微鏡空間分辨率太低，并需要給樣本脫水；自然的拉曼顯微鏡需要很高的激光能量，整體耗時(shí)很長(zhǎng)，在活樣本中的應(yīng)用受到限制；相干反斯托克拉曼散射顯微鏡在拍攝除了脂質(zhì)以外的大多數(shù)分子時(shí)對(duì)比度不夠，而新型SRS顯微鏡都能突破這些局限。研究人員表示，新型SRS顯微鏡在醫(yī)療領(lǐng)域的應(yīng)用前景廣闊。比如，手術(shù)之前必須將樣本送檢以用于組織分析，這個(gè)過(guò)程大約要花20分鐘，其間病人需要等在手術(shù)臺(tái)上，而新技術(shù)可提供實(shí)時(shí)掃描透視，有助于加速外科手術(shù)，清除腫瘤和其他損傷。謝曉亮說(shuō)：“這一項(xiàng)目開(kāi)始于11年前，核磁共振技術(shù)花了30多年才用于臨床，我們期望這種SRS顯微鏡盡早應(yīng)用于醫(yī)院?！眮?lái)源：科技日?qǐng)?bào) 常麗君

【點(diǎn)評(píng)】
　　該項(xiàng)技術(shù)將會(huì)極大的促進(jìn)生理生化尤其是新陳代謝的研究，如能成熟地運(yùn)用于人體，對(duì)于人體生理學(xué)及醫(yī)學(xué)研究將有巨大的幫助。

【原文摘錄】 Science Vol. 330 no. 6009 pp. 1368-1370 DOI: 10.1126/science.1197236
Video-Rate Molecular Imaging in Vivo with Stimulated Raman Scattering
Brian G. Saar1,Christian W. Freudiger, Jay Reichman, et al.
Optical imaging in vivo with molecular specificity is important in biomedicine because of its high spatial resolution and sensitivity compared with magnetic resonance imaging. Stimulated Raman scattering (SRS) microscopy allows highly sensitive optical imaging based on vibrational spectroscopy without adding toxic or perturbative labels. However, SRS imaging in living animals and humans has not been feasible because light cannot be collected through thick tissues, and motion-blur arises from slow imaging based on backscattered light. In this work, we enable in vivo SRS imaging by substantially enhancing the collection of the backscattered signal and increasing the imaging speed by three orders of magnitude to video rate. This approach allows label-free in vivo imaging of water, lipid, and protein in skin and mapping of penetration pathways of topically applied drugs in mice and humans.

4.  果蠅激活生殖細(xì)胞遺傳基因來(lái)產(chǎn)生腫瘤
【摘要】  
　　巴塞羅那的 科學(xué)家近日在Science上報(bào)道他們發(fā)現(xiàn)了果蠅幼蟲利用生殖細(xì)胞的遺傳程序來(lái)催生腦部腫瘤。關(guān)閉涉及到的相關(guān)基因就會(huì)保持健康的大腦，這是首次發(fā)現(xiàn)關(guān)閉這些相關(guān)基因可以使果蠅腦部腫瘤消失。說(shuō)明這些生殖細(xì)胞的遺傳基因?qū)τ诖祟惸[瘤的發(fā)生有關(guān)鍵作用。此前十年積累的數(shù)據(jù)顯示某些腫瘤如黑色素瘤和某些類癌的癌細(xì)胞會(huì)激活生殖細(xì)胞的遺傳基因。

【點(diǎn)評(píng)】
　　這項(xiàng)研究說(shuō)明癌基因并不一定是癌癥發(fā)生的原因，生殖基因的激活也可能引發(fā)癌癥。基因激活的生理調(diào)控是否正常是很重要的。

【原文摘錄】 Science, December 23, 2010 DOI: 10.1126/science.1195481
Ectopic expression of germline genes drives malignant brain tumor growth in Drosophila.
Janic A, Mendizabal L, Llamazares S, Rossell D, Gonzalez C.
Model organisms such as the fruit fly Drosophila melanogaster can help to elucidate the molecular basis of complex diseases such as cancer. Mutations in the Drosophila gene lethal (3) malignant brain tumor cause malignant growth in the larval brain. Here we show that l(3)mbt tumors exhibited a soma-to-germline transformation through the ectopic expression of genes normally required for germline stemness, fitness, or longevity. Orthologs of some of these genes were also expressed in human somatic tumors. In addition, inactivation of any of the germline genes nanos, vasa, piwi, or aubergine suppressed l(3)mbt malignant growth. Our results demonstrate that germline traits are necessary for tumor growth in this Drosophila model and suggest that inactivation of germline genes might have tumor-suppressing effects in other species.

5.  癌細(xì)胞自我毀滅與自我保護(hù)的信號(hào)分子
【摘要】
　　斯坦福大學(xué)醫(yī)學(xué)院的研究人員發(fā)現(xiàn)許多癌細(xì)胞自身帶有自我毀滅的種子--細(xì)胞表面一種名為鈣網(wǎng)素的蛋白—能召集循環(huán)系統(tǒng)的巨噬細(xì)胞來(lái)吞食消化他們。而絕大多數(shù)癌細(xì)胞沒(méi)有被毀滅是因?yàn)樗麄兺瑫r(shí)表達(dá)另一種信號(hào)蛋白CD47對(duì)抗鈣網(wǎng)素的作用。

【點(diǎn)評(píng)】
　　CD47與鈣網(wǎng)素的作用及二者平衡的調(diào)節(jié)會(huì)促進(jìn)癌癥免疫療法的發(fā)展。

【原文摘錄】 Sci Transl Med 22 December 2010: Vol. 2, Issue 63, p. 63ra94
Calreticulin Is the Dominant Pro-Phagocytic Signal on Multiple Human Cancers and Is Counterbalanced by CD47
M. P. Chao, S. Jaiswal, R. Weissman-Tsukamoto, et al.
Under normal physiological conditions, cellular homeostasis is partly regulated by a balance of pro- and anti-phagocytic signals. CD47, which prevents cancer cell phagocytosis by the innate immune system, is highly expressed on several human cancers including acute myeloid leukemia, non-Hodgkin’s lymphoma, and bladder cancer. Blocking CD47 with a monoclonal antibody results in phagocytosis of cancer cells and leads to in vivo tumor elimination, yet normal cells remain mostly unaffected. Thus, we postulated that cancer cells must also display a potent pro-phagocytic signal. Here, we identified calreticulin as a pro-phagocytic signal that was highly expressed on the surface of several human cancers, but was minimally expressed on most normal cells. Increased CD47 expression correlated with high amounts of calreticulin on cancer cells and was necessary for protection from calreticulin-mediated phagocytosis. Blocking the interaction of target cell calreticulin with its receptor, low-density lipoprotein receptor–related protein, on phagocytic cells prevented anti-CD47 antibody–mediated phagocytosis. Furthermore, increased calreticulin expression was an adverse prognostic factor in diverse tumors including neuroblastoma, bladder cancer, and non-Hodgkin’s lymphoma. These findings identify calreticulin as the dominant pro-phagocytic signal on several human cancers, provide an explanation for the selective targeting of tumor cells by anti-CD47 antibody, and highlight the balance between pro- and anti-phagocytic signals in the immune evasion of cancer.

6. 微小RNA表達(dá)模式的整體圖譜區(qū)分干細(xì)胞類別
【摘要】
　　干細(xì)胞生物學(xué)在全世界引發(fā)人們對(duì)其可以最終修復(fù)身體部位的巨大期望。盡管很多科學(xué)家認(rèn)為這是可行的，但是必須克服很多障礙，包括令人擔(dān)憂的在修復(fù)器官時(shí)引發(fā)癌癥的潛在風(fēng)險(xiǎn)。而近日?qǐng)?bào)道的加州大學(xué)的一項(xiàng)關(guān)于多能性干細(xì)胞的微小RNA表達(dá)模式的研究或許對(duì)此有所幫助。他們分析很多種多能性干細(xì)胞的微小RNA表達(dá)模式，發(fā)現(xiàn)所有的多能性干細(xì)胞微小RNA表達(dá)模式并不相同，但不是因細(xì)胞來(lái)源而異，而是具有不同的p53 體系狀態(tài)。微小RNA表達(dá)模式的整體圖譜能夠告訴你這是何種細(xì)胞，何種癌癥，是否干細(xì)胞等信息。

【點(diǎn)評(píng)】
　　微小RNA表達(dá)模式的整體圖譜研究也許會(huì)有助于研究人體潛能再生細(xì)胞的定位和屬性。

【原文摘錄】 Cell Stem Cell, Volume 7, Issue 6, 671-681, 3 December 2010
MicroRNA Profiling Reveals Two Distinct p53-Related Human Pluripotent Stem Cell States
Pierre Neveu, Min Jeong Kye, Shuping Qi, et al.
Highlights
miRNA profiles distinguish two categories of human pluripotent stem cells
The p53 network status distinguishes pluripotent cells independently of their origin
p53-targeting miRNAs change the classification status of iPSCs
A 2D representation of miRNA profiles tracks differentiation and reprogramming
Summary
Reprogramming methodologies have provided multiple routes for achieving pluripotency. However, pluripotency is generally considered to be an almost singular state, with subtle differences described between induced pluripotent stem cells (iPSCs) and embryonic stem cells (ESCs). We profiled miRNA expression levels across 49 human cell lines, including ESCs, iPSCs, differentiated cells, and cancer cell lines. We found that the resulting miRNA profiles divided the iPSCs and hESCs examined into two distinct categories irrespective of the cell line origin. The miRNAs that defined these two pluripotency categories also distinguished cancer cells from differentiated cells. Transcriptome analysis suggested that several gene sets related to p53 distinguished these categories, and overexpression of the p53-targeting miRNAs miR-92 and miR-141 in iPSCs was sufficient to change their classification status. Thus, our results suggest a subdivision of pluripotent stem cell states that is independent of their origin but related to p53 network status.

7. 2010再生科學(xué)年度進(jìn)展
　　根據(jù)與人體再生復(fù)原科學(xué)的相關(guān)程度，本年度登載的以下動(dòng)態(tài)作為2010再生科學(xué)年度進(jìn)展：

1.人體多能干細(xì)胞體外定向分化形成腸組織；
2.老鼠實(shí)驗(yàn)表明修復(fù)端粒可以逆轉(zhuǎn)衰老；
3.蠑螈重生肢體和器官的獨(dú)特酶；
4.生長(zhǎng)因子TGF-β2和BMP4可使成熟細(xì)胞轉(zhuǎn)化為成人干細(xì)胞；
5.生命復(fù)雜性的產(chǎn)生可能必須先有線粒體出現(xiàn)；
6.黃芩湯可減輕腸癌患者化療損傷；
7.細(xì)胞生長(zhǎng)調(diào)控依靠細(xì)胞質(zhì)核傳輸；
8.洞螈長(zhǎng)壽研究或解開(kāi)衰老之謎；
9.脂肪可用作細(xì)胞內(nèi)在pH感受器；
10.發(fā)現(xiàn)上皮組織中神秘免疫細(xì)胞的功能和機(jī)理；
11.細(xì)胞歸巢法使兔滑膜關(guān)節(jié)面再生；
12.控制細(xì)胞分化的力學(xué)因素；
13.關(guān)鍵基因控制哺乳動(dòng)物組織再生；
14.細(xì)胞運(yùn)動(dòng)的集體調(diào)控控制胚胎的生長(zhǎng)；
15.首次發(fā)現(xiàn)可發(fā)育成卵的干細(xì)胞;
16.精子形成過(guò)程中的細(xì)胞在一定時(shí)期內(nèi)可以變回干細(xì)胞；
17.“活體生物反應(yīng)器”“原位”培養(yǎng)再生新器官；
18.發(fā)現(xiàn)斑馬魚造血干細(xì)胞生成機(jī)理。