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2015年2月15日訊 /生物谷BIOON/ --一直以來，科學(xué)家們都希望從根源上認(rèn)識白血病的致病機理。最近來自微軟公司和劍橋大學(xué)的研究人員們構(gòu)建了一個電腦模型用于模擬血細胞的整個發(fā)育過程。這也使模擬白血病相關(guān)基因在血細胞發(fā)育過程中是如何表達并最終導(dǎo)致白血病發(fā)生成為了可能。這一方法為今后的研究人員更好認(rèn)識白血病以及其他血液疾病的致病機理提供了一個更便捷的工具。 在最近一期的Nature Biotechnology中，微軟和劍橋大學(xué)的科學(xué)家介紹他們首先測定了3900個造血干細胞的基因活性，并將獲得的數(shù)據(jù)進行綜合構(gòu)建出了一個模型?？茖W(xué)家聲稱利用這個模型，研究人員能夠進行一些簡單、快速的模擬實驗，而在實驗室中這些實驗一般耗時長達數(shù)周之久。例如在關(guān)于Hox和Sox兩種基因在白血病發(fā)生中所扮演的角色上，這種新型的模型預(yù)測結(jié)果與實驗結(jié)果就達到了良好的一致性。 研究人員希望今后這種模型能夠用于更多疾病的研究上。（生物谷Bioon.com） 生物谷推薦的英文摘要：
Nature Biotechnology Decoding the regulatory network of early blood development from single-cell gene expression measurements Victoria Moignard, Steven Woodhouse, Laleh Haghverdi, Andrew J Lilly, Yosuke Tanaka, Adam C Wilkinson, Florian Buettner, Iain C Macaulay, Wajid Jawaid, Evangelia Diamanti, Shin-Ichi Nishikawa, Nir Piterman, Valerie Kouskoff, Fabian J Theis, Jasmin Fisher & Berthold G?ttgens Reconstruction of the molecular pathways controlling organ development has been hampered by a lack of methods to resolve embryonic progenitor cells. Here we describe a strategy to address this problem that combines gene expression profiling of large numbers of single cells with data analysis based on diffusion maps for dimensionality reduction and network synthesis from state transition graphs. Applying the approach to hematopoietic development in the mouse embryo, we map the progression of mesoderm toward blood using single-cell gene expression analysis of 3,934 cells with blood-forming potential captured at four time points between E7.0 and E8.5. Transitions between individual cellular states are then used as input to develop a single-cell network synthesis toolkit to generate a computationally executable transcriptional regulatory network model of blood development. Several model predictions concerning the roles of Sox and Hox factors are validated experimentally. Our results demonstrate that single-cell analysis of a developing organ coupled with computational approaches can reveal the transcriptional programs that underpin organogenesis. |
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