Cellular Heterogeneity and Lineage Restriction during Mouse Digit Tip Regeneration at Single-Cell Resolution.,Developmental Cell

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Cellular Heterogeneity and Lineage Restriction during Mouse Digit Tip Regeneration at Single-Cell Resolution.
Developmental Cell ( IF 10.7 ) Pub Date : 2020-02-24 , DOI: 10.1016/j.devcel.2020.01.026
Gemma L Johnson ₁ , Erick J Masias ₂ , Jessica A Lehoczky ₂

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Innate regeneration following digit tip amputation is one of the few examples of epimorphic regeneration in mammals. Digit tip regeneration is mediated by the blastema, the same structure invoked during limb regeneration in some lower vertebrates. By genetic lineage analyses, the digit tip blastema has been defined as a population of heterogeneous, lineage-restricted progenitor cells. These previous studies, however, do not comprehensively evaluate blastema heterogeneity or address lineage restriction of closely related cell types. In this report, we present single-cell RNA sequencing of over 38,000 cells from mouse digit tip blastemas and unamputated control digit tips and generate an atlas of the cell types participating in digit tip regeneration. We computationally define differentiation trajectories of vascular, monocytic, and fibroblastic lineages over regeneration, and while our data confirm broad lineage restriction of progenitors, our analysis reveals 67 genes enriched in blastema fibroblasts including a novel regeneration-specific gene, Mest.

中文翻译：

单细胞分辨率下小鼠指尖再生过程中的细胞异质性和谱系限制。

指尖截肢后的先天再生是哺乳动物中为数不多的外貌再生的例子之一。指尖再生是由芽基介导的，与一些低等脊椎动物的肢体再生过程中所调用的结构相同。通过遗传谱系分析，指尖胚基被定义为异质的、谱系限制的祖细胞群。然而，这些先前的研究没有全面评估胚基异质性或解决密切相关的细胞类型的谱系限制。在本报告中，我们对来自小鼠指尖胚基和未截肢的对照指尖的 38,000 多个细胞进行了单细胞 RNA 测序，并生成了参与指尖再生的细胞类型图谱。我们通过计算定义了血管、单核细胞和成纤维细胞谱系在再生过程中的分化轨迹，虽然我们的数据证实了祖细胞的广泛谱系限制，但我们的分析揭示了胚基成纤维细胞中富集的 67 个基因，包括一种新的再生特异性基因 Mest。

更新日期：2020-02-24

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