Parallel Single-Cell Multiomics Analysis of Neonatal Skin Reveals the Transitional Fibroblast States that Restrict Differentiation into Distinct Fates.
Parallel Single-Cell Multiomics Analysis of Neonatal Skin Reveals the Transitional Fibroblast States that Restrict Differentiation into Distinct Fates.
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DOI：
10.1016/j.jid.2021.11.032
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发表时间：
2022-07
影响因子：
6.5
通讯作者：
Driskell, Ryan R.
中科院分区：
文献类型：
--
作者：
Thompson, Sean M.;Phan, Quan M.;Winuthayanon, Sarayut;Driskell, Iwona M.;Driskell, Ryan R.
实现皮肤再生的关键之一在于了解支持皮肤再生的新生儿成纤维细胞的异质性。然而，调节这些细胞的细胞状态和命运的分子基础尚未完全了解。为了研究这一点，我们通过处理新生鼠皮肤分别进行单细胞ATAC测序（scATAC-seq）和单细胞RNA测序（scRNA-seq）来进行平行的多组学分析。我们的方法显示，成纤维细胞簇可以根据转录组谱分为乳头状和网状谱系，如先前发表的。然而，新生儿成纤维细胞谱系标志物（如Dpp 4/CD 26、Corin和Dlk 1沿着肌成纤维细胞标志物）的scATAC-seq分析显示，尽管其谱系特异性转录组谱，但在所有成纤维细胞群体中均存在可接近的染色质。这些结果表明，可接近的染色质并不总是转化为基因表达，许多成纤维细胞谱系标志物反映成纤维细胞状态，包括新生儿乳头状，网状和肌成纤维细胞。这一分析也提供了一个可能的解释，为什么这些标记基因可以混杂表达在不同的成纤维细胞群体在不同的条件下。我们的scATAC-seq分析还揭示了毛乳头和脂肪细胞命运之间的功能谱系限制由不同的染色质景观调节。最后，我们为我们的多组学分析开发了一个网络工具：https://skinregeneration.org/scatacseq-and-scrnaseq-data-from-thompson-et-al-2021-2/。
One of the keys to achieving skin regeneration lies within understanding the heterogeneity of neonatal fibroblasts, which support skin regeneration. However, the molecular underpinnings regulating the cellular states and fates of these cells are not fully understood. To investigate this, we performed a parallel multi-omics analysis by processing neonatal murine skin for single-cell ATAC-sequencing (scATAC-seq) and single-cell RNA-sequencing (scRNA-seq) separately. Our approach revealed that fibroblast clusters could be sorted into papillary and reticular lineages based on transcriptome profiling, as previously published. However, scATAC-seq analysis of neonatal fibroblast lineage markers, such as, Dpp4/CD26, Corin, and Dlk1 along with markers of myofibroblasts, revealed accessible chromatin in all fibroblast populations despite their lineage-specific transcriptome profiles. These results suggests that accessible chromatin does not always translate to gene expression and that many fibroblast lineage markers reflect a fibroblast state, which includes neonatal papillary, reticular, and myofibroblasts. This analysis also provides a possible explanation as to why these marker genes can be promiscuously expressed in different fibroblast populations under different conditions. Our scATAC-seq analysis also revealed that the functional lineage restriction between dermal papilla and adipocyte fates are regulated by distinct chromatin landscapes. Finally, we have developed a webtool for our multi-omics analysis: https://skinregeneration.org/scatacseq-and-scrnaseq-data-from-thompson-et-al-2021-2/.
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影响因子：
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通讯作者：
Greenleaf WJ