Single Cell RNA Sequencing Reveals Critical Functions of Mkx in Periodontal Ligament Homeostasis.

Single Cell RNA Sequencing Reveals Critical Functions of Mkx in Periodontal Ligament Homeostasis.
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DOI:
10.3389/fcell.2022.795441
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发表时间:
2022
影响因子:
5.5
通讯作者:
Asahara H
Asahara H
中科院分区:
生物学2区
文献类型:
--
作者:
Takada K;Chiba T;Miyazaki T;Yagasaki L;Nakamichi R;Iwata T;Moriyama K;Harada H;Asahara H

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牙周韧带(PDL)由连接牙齿和牙槽骨的纤维组织组成,对牙周功能至关重要。转录因子莫霍克同源盒(mohawk homeobox, Mkx)在PDL中表达,在PDL的发育和维持中起重要作用。然而,Mkx在组成PDL的细胞群中的精确和关键功能尚未阐明。本研究旨在利用单细胞RNA测序技术阐明Mkx缺乏对野生型(WT) (Mkx +/+)和Mkx敲除(Mkx−/−)大鼠PDL细胞异质性的影响以及PDL组织中基因表达的差异。我们鉴定了12个细胞簇,包括间充质细胞和巨噬细胞。Mkx和sclaxis (Scx, PDL的另一个关键转录因子)的表达是互斥的,并将间充质细胞团划分为Mkx和Scx型,分别主要表达蛋白聚糖和弹性纤维,以及1型和3型胶原。在Mkx−/−多于Mkx +/+ pdl的间充质细胞和成骨细胞簇中,骨化相关基因表达上调。Mkx−/−PDL的巨噬细胞簇中细胞和炎症介质数量增加。这些结果表明,Mkx通过调节特定细胞群和基因表达,在维持PDL稳态中起重要作用。
The periodontal ligament (PDL) comprises a fibrous tissue that connects teeth to alveolar bone and is essential for periodontal function. The transcription factor mohawk homeobox (Mkx) is expressed in the PDL where it plays an important role in the development and maintenance of the PDL. However, the precise and critical functions of Mkx in the cell populations comprising PDL have not yet been elucidated. The present study aimed to clarify the effects of a Mkx deficiency on PDL cellular heterogeneity and differences between gene expression in PDL tissues from wild-type (WT) (Mkx +/+ ) and Mkx knockout (Mkx −/− ) rats using single-cell RNA sequencing. We identified 12 cell clusters comprising mesenchymal cells and macrophages. The expression of Mkx and scleraxis (Scx; another key transcription factor of PDL), was mutually exclusive, and partitioned mesenchymal cell clusters into Mkx and Scx types that dominantly expressed proteoglycans and elastic fibers, and type 1 and 3 collagen, respectively. Ossification-related genes were upregulated in mesenchymal cell and osteoblast clusters with more Mkx −/− than Mkx +/+ PDLs. Increased number of cells and inflammatory mediators were observed in macrophage clusters of Mkx −/− PDL. These results suggested that Mkx plays an important role in maintaining PDL homeostasis by regulating specific cell populations and gene expression.
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