Pantalacci Sophie, Guéguen Laurent, Petit Coraline, Lambert Anne, Peterkovà Renata, Sémon Marie
UnivLyon, ENS de Lyon, Univ Claude Bernard, CNRS UMR 5239, INSERM U1210, Laboratoire de Biologie et Modélisation de la Cellule, 15 parvis Descartes, F-69007, Lyon, France.
Laboratoire de Biométrie et Biologie Évolutive (LBBE), Université de Lyon, Université Lyon 1, CNRS, Villeurbanne, France.
Genome Biol. 2017 Feb 15;18(1):29. doi: 10.1186/s13059-017-1157-7.
Comparative transcriptomics can answer many questions in developmental and evolutionary developmental biology. Most transcriptomic studies start by showing global patterns of variation in transcriptomes that differ between species or organs through developmental time. However, little is known about the kinds of expression differences that shape these patterns.
We compared transcriptomes during the development of two morphologically distinct serial organs, the upper and lower first molars of the mouse. We found that these two types of teeth largely share the same gene expression dynamics but that three major transcriptomic signatures distinguish them, all of which are shaped by differences in the relative abundance of different cell types. First, lower/upper molar differences are maintained throughout morphogenesis and stem from differences in the relative abundance of mesenchyme and from constant differences in gene expression within tissues. Second, there are clear time-shift differences in the transcriptomes of the two molars related to cusp tissue abundance. Third, the transcriptomes differ most during early-mid crown morphogenesis, corresponding to exaggerated morphogenetic processes in the upper molar involving fewer mitotic cells but more migrating cells. From these findings, we formulate hypotheses about the mechanisms enabling the two molars to reach different phenotypes. We also successfully applied our approach to forelimb and hindlimb development.
Gene expression in a complex tissue reflects not only transcriptional regulation but also abundance of different cell types. This knowledge provides valuable insights into the cellular processes underpinning differences in organ development. Our approach should be applicable to most comparative developmental contexts.
比较转录组学能够回答发育生物学和进化发育生物学中的许多问题。大多数转录组学研究首先展示的是，在发育过程中，不同物种或器官的转录组之间存在的整体变异模式。然而，对于形成这些模式的表达差异类型，我们却知之甚少。
我们比较了小鼠上下颌第一磨牙这两种形态上不同的连续器官在发育过程中的转录组。我们发现，这两种类型的牙齿在很大程度上共享相同的基因表达动态，但有三个主要的转录组特征将它们区分开来，所有这些特征都由不同细胞类型的相对丰度差异所塑造。第一，下颌/上颌磨牙的差异在整个形态发生过程中都存在，源于间充质相对丰度的差异以及组织内基因表达的持续差异。第二，与尖部组织丰度相关的两个磨牙转录组存在明显的时间偏移差异。第三，转录组在冠部早期到中期形态发生过程中差异最大，这对应于上颌磨牙中夸张的形态发生过程，涉及较少的有丝分裂细胞但更多的迁移细胞。基于这些发现，我们提出了关于使两个磨牙达到不同表型的机制的假设。我们还成功地将我们的方法应用于前肢和后肢的发育。
复杂组织中的基因表达不仅反映转录调控，还反映不同细胞类型的丰度。这一知识为理解器官发育差异背后的细胞过程提供了有价值的见解。我们的方法应该适用于大多数比较发育的情况。
