System-level analyses of keystone genes required for mammalian tooth development.
System-level analyses of keystone genes required for mammalian tooth development.
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DOI：
10.1002/jez.b.23009
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发表时间：
2021-01
期刊：
影响因子：
--
通讯作者：
Jernvall J
中科院分区：
文献类型：
--
作者：
Hallikas O;Das Roy R;Christensen MM;Renvoisé E;Sulic AM;Jernvall J
当基因的无效突变导致发育完全停滞时，该基因通常被认为对生命至关重要。然而，在大多数情况下，无效突变对表型有更微妙的影响。在这里，我们使用突变的表型严重性作为工具来检查基因表达的系统水平动态。我们将小鼠磨牙正常发育所需的基因分为不同的类别，从必需的到微妙的表型修饰。总的来说，我们称之为发育关键基因。使用微阵列和RNAseq分析模式化阶段小鼠磨牙的转录组分析显示，牙齿发育进程所必需的基因的表达水平高度升高，这一结果让人想起单细胞生物体中的必需基因。在发育中的大鼠磨牙中也检测到进展基因的表达水平升高，这表明这种系统水平的动态进化保守。对发育中小鼠磨牙的单细胞RNAseq分析表明，尽管以细胞数量衡量的表达结构域的大小是器官水平表达的主要驱动因素，但进展基因显示出高细胞水平的转录丰度。进展基因也在其途径内上调，其本身高度表达。相比之下，正常牙齿形成所需的高比例基因是分泌配体，其在比其受体和细胞内组分更少的细胞中表达。总体而言，即使单个基因的表达模式可能高度不同，但可以使用表型定义的基因类别检测基因表达的保守系统水平原则。一个分类方案的构建所需的基因的发展，小鼠磨牙，其次是基因表达分析的分类。 小鼠牙齿突变的表型严重程度用于对基因进行分类。牙发生过程中的重要基因在器官和细胞水平上高度表达。正常模式化所需的许多基因是局部表达的配体。
When a null mutation of a gene causes a complete developmental arrest, the gene is typically considered essential for life. Yet, in most cases, null mutations have more subtle effects on the phenotype. Here we used the phenotypic severity of mutations as a tool to examine system‐level dynamics of gene expression. We classify genes required for the normal development of the mouse molar into different categories that range from essential to subtle modification of the phenotype. Collectively, we call these the developmental keystone genes. Transcriptome profiling using microarray and RNAseq analyses of patterning stage mouse molars show highly elevated expression levels for genes essential for the progression of tooth development, a result reminiscent of essential genes in single‐cell organisms. Elevated expression levels of progression genes were also detected in developing rat molars, suggesting evolutionary conservation of this system‐level dynamics. Single‐cell RNAseq analyses of developing mouse molars reveal that even though the size of the expression domain, measured in the number of cells, is the main driver of organ‐level expression, progression genes show high cell‐level transcript abundances. Progression genes are also upregulated within their pathways, which themselves are highly expressed. In contrast, a high proportion of the genes required for normal tooth patterning are secreted ligands that are expressed in fewer cells than their receptors and intracellular components. Overall, even though expression patterns of individual genes can be highly different, conserved system‐level principles of gene expression can be detected using phenotypically defined gene categories. A classification scheme is constructed for genes required for the development of mouse molar teeth, followed by gene expression analyses of the classifications. The phenotypic severity of mutations on mouse teeth is used to classify genes. Genes essential for the progression of odontogenesis are highly expressed at the organ and cell level. Many of the genes required for normal patterning are locally expressed ligands.
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DOI：
10.1093/bioinformatics/btu638
发表时间：
2015-01-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Anders S;Pyl PT;Huber W
通讯作者：
Huber W
校正的肌肉校准力精度在啮齿动物的分子树中精确的放置。
影响因子：
4.6
作者：
Kimura Y;Hawkins MT;McDonough MM;Jacobs LL;Flynn LJ
通讯作者：
Flynn LJ
AfterQC：fastq数据的自动过滤、修剪、错误消除和质量控制
影响因子：
3
作者：
Chen S;Huang T;Zhou Y;Han Y;Xu M;Gu J
通讯作者：
Gu J
影响因子：
64.8
作者：
Dickinson ME;Flenniken AM;Ji X;Teboul L;Wong MD;White JK;Meehan TF;Weninger WJ;Westerberg H;Adissu H;Baker CN;Bower L;Brown JM;Caddle LB;Chiani F;Clary D;Cleak J;Daly MJ;Denegre JM;Doe B;Dolan ME;Edie SM;Fuchs H;Gailus-Durner V;Galli A;Gambadoro A;Gallegos J;Guo S;Horner NR;Hsu CW;Johnson SJ;Kalaga S;Keith LC;Lanoue L;Lawson TN;Lek M;Mark M;Marschall S;Mason J;McElwee ML;Newbigging S;Nutter LM;Peterson KA;Ramirez-Solis R;Rowland DJ;Ryder E;Samocha KE;Seavitt JR;Selloum M;Szoke-Kovacs Z;Tamura M;Trainor AG;Tudose I;Wakana S;Warren J;Wendling O;West DB;Wong L;Yoshiki A;International Mouse Phenotyping Consortium;Jackson Laboratory;Infrastructure Nationale PHENOMIN, Institut Clinique de la Souris (ICS);Charles River Laboratories;MRC Harwell;Toronto Centre for Phenogenomics;Wellcome Trust Sanger Institute;RIKEN BioResource Center;MacArthur DG;Tocchini-Valentini GP;Gao X;Flicek P;Bradley A;Skarnes WC;Justice MJ;Parkinson HE;Moore M;Wells S;Braun RE;Svenson KL;de Angelis MH;Herault Y;Mohun T;Mallon AM;Henkelman RM;Brown SD;Adams DJ;Lloyd KC;McKerlie C;Beaudet AL;Bućan M;Murray SA
通讯作者：
Murray SA
影响因子：
64.8
作者：
Harjunmaa, Enni;Kallonen, Aki;Jernvall, Jukka
通讯作者：
Jernvall, Jukka