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Nature:如何利用单细胞mRNA测序发现罕见细胞类型?

2015-08-25 佚名 生物谷

近日,来自荷兰的科学家在著名国际学术期刊nature上发表了一项最新研究进展,他们利用一种新的计算方法结合转录组测序发现了小肠中一些罕见的细胞类型,这对于深入了解器官的细胞组成,探究健康和疾病状态下的组织生物学具有重要意义。 理解一个器官的发育和功能需要对组成该器官的所有细胞类型的特性有一个清晰的认识。传统发现认为分离细胞亚群的方法是基于几个已知的标记基因表达出来的信使RNA或蛋白质实现


近日,来自荷兰的科学家在著名国际学术期刊nature上发表了一项最新研究进展,他们利用一种新的计算方法结合转录组测序发现了小肠中一些罕见的细胞类型,这对于深入了解器官的细胞组成,探究健康和疾病状态下的组织生物学具有重要意义。
 
理解一个器官的发育和功能需要对组成该器官的所有细胞类型的特性有一个清晰的认识。传统发现认为分离细胞亚群的方法是基于几个已知的标记基因表达出来的信使RNA或蛋白质实现的。但是对于一些罕见的细胞类型来说,鉴定出它们特定的标记基因目前仍存在很大挑战。而发现一些罕见的细胞类型,如干细胞,短暂存在的前体细胞,癌症干细胞或循环肿瘤细胞,对于深入理解正常和疾病状态下的组织生物学具有非常重要的意义。
 
为解决这一问题,研究人员首先从培养的小肠类器官中随机挑选了几百种不同的细胞类型进行转录组测序,这种培养的小肠类器官包含了哺乳动物小肠所有的细胞谱系。由于目前可用的计算方法只能对一些丰度较高的细胞类型进行确定,因此研究人员开发了一种叫做RaceID的算法,用于在复杂的单细胞群体中发现一些罕见的细胞类型。
 
研究人员利用这种计算方法发现Reg4是一种罕见的肠内分泌细胞的新标记基因,随后他们利用Reg4富集这种罕见细胞,检测这一细胞群体的异质性,结果表明这群细胞中存在已知的肠内分泌细胞谱系,同时还发现了一些新的细胞亚型。在对RaceID这一算法进行了验证之后,研究人员又利用这一算法分离了Lgr5阳性的干细胞以及由这些细胞形成的后代细胞,结果表明Lgr5阳性细胞代表了一群同种的丰度较高的干细胞群体,同时混杂了一种罕见的Lgr5阳性的分泌细胞群。
 
这项研究通过开发一种算法分析转录组测序结果,能够在复杂的单细胞群体中发现一些罕见的细胞类型及其特定标记基因,对于了解正常的和疾病状态下的组织生物学具有重要意义。

原文出处:
 
Dominic Grün,Anna Lyubimova.et al.Single-cell messenger RNA sequencing reveals rare intestinal cell types.nature.2015

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    2016-04-01 liye789132251
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    2015-08-27 syscxl
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    2015-08-25 1ddb5eeam46(暂无匿称)

    什么计算方法?怎么算的?

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