Single cell RNA-sequencing reveals cellular heterogeneity and trajectories of lineage specification during murine embryonic limb development
Single cell RNA-sequencing reveals cellular heterogeneity and trajectories of lineage specification during murine embryonic limb development
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DOI：
10.1016/j.matbio.2019.12.004
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发表时间：
2020-07-01
期刊：
影响因子：
6.9
通讯作者：
Guilak, Farshid
中科院分区：
文献类型：
--
作者：
Kelly, Natalie H.;Huynh, Nguyen P. T.;Guilak, Farshid
小鼠后肢基因表达的时空协调调控决定了间充质祖细胞的同一性及其形成的肌肉骨骼组织的多样性发育。历史上，后肢发育的研究一直是通过对先天选择的单个基因进行谱系追踪，或者在整体组织水平上进行谱系追踪，这并不允许确定产生成熟细胞类型和组织的单细胞转录程序。为了确定肢体芽发育过程中谱系规范的细胞轨迹，我们使用单细胞mRNA测序（scRNA-seq）分析了胚胎期(E)11.5-E18.5之间发育中的小鼠后肢。我们在所有时间点都发现了细胞类型的异质性，以及形成小鼠后肢的预期细胞类型。此外，我们使用RNA荧光原位杂交（FISH）来检查细胞类型和细胞轨迹的空间位置，以了解细胞成熟的祖先连续体。这些数据为后肢发育的转录程序提供了资源，将支持未来肌肉骨骼发育的研究，并产生组织再生的假设。(C) 2019 Elsevier B.V.版权所有
The coordinated spatial and temporal regulation of gene expression in the murine hindlimb determines the identity of mesenchymal progenitors and the development of diversity of musculoskeletal tissues they form. Hindlimb development has historically been studied with lineage tracing of individual genes selected a priori, or at the bulk tissue level, which does not allow for the determination of single cell transcriptional programs yielding mature cell types and tissues. To identify the cellular trajectories of lineage specification during limb bud development, we used single cell mRNA sequencing (scRNA-seq) to profile the developing murine hindlimb between embryonic days (E)11.5-E18.5. We found cell type heterogeneity at all time points, and the expected cell types that form the mouse hindlimb. In addition, we used RNA fluorescence in situ hybridization (FISH) to examine the spatial locations of cell types and cell trajectories to understand the ancestral continuum of cell maturation. This data provides a resource for the transcriptional program of hindlimb development that will support future studies of musculoskeletal development and generate hypotheses for tissue regeneration. (C) 2019 Elsevier B.V. All rights reserved.