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2015年2月15日讯 /生物谷BIOON/ --一直以来，科学家们都希望从根源上认识白血病的致病机理。最近来自微软公司和剑桥大学的研究人员们构建了一个电脑模型用于模拟血细胞的整个发育过程。这也使模拟白血病相关基因在血细胞发育过程中是如何表达并最终导致白血病发生成为了可能。这一方法为今后的研究人员更好认识白血病以及其他血液疾病的致病机理提供了一个更便捷的工具。 在最近一期的Nature Biotechnology中，微软和剑桥大学的科学家介绍他们首先测定了3900个造血干细胞的基因活性，并将获得的数据进行综合构建出了一个模型。科学家声称利用这个模型，研究人员能够进行一些简单、快速的模拟实验，而在实验室中这些实验一般耗时长达数周之久。例如在关于Hox和Sox两种基因在白血病发生中所扮演的角色上，这种新型的模型预测结果与实验结果就达到了良好的一致性。 研究人员希望今后这种模型能够用于更多疾病的研究上。（生物谷Bioon.com） 生物谷推荐的英文摘要：
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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来自： 昵称21979920 > 《一般进展性研究》
