LncRNA Meg3-mediated regulation of the Smad pathway in atRA-induced cleft palate

Liu, Xiaozhuan; Zhang, Yuwei; Shen, Lijun; He, Zhidong; Chen, Yao; Li, Ning; Zhang, Xiuli; Zhang, Tingting; Gao, Suhua; Yue, Haodi; Li, Zhitao; Yu, Zengli

doi:10.1016/j.toxlet.2021.01.017

Cited by 11 publications

(8 citation statements)

References 39 publications

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“…We reviewed all the lncRNAs in the literature to figure out the lncRNAs associated with mammalian palatogenesis. Surprisingly, only three lncRNAs ( H19 , Meg3 , and Xist ) have been known to be associated with mammalian palatogenesis (Gao et al., 2017b; Liu et al., 2021; Yeung et al., 2014). According to the analyses in this study, we propose that biological processes including adhesion, cilia, and bone‐related process are important in palatal development.…”

Section: Resultsmentioning

confidence: 99%

Time‐series expression profiles of mRNAs and lncRNAs during mammalian palatogenesis

Huang

Zhong

et al. 2022

Oral Diseases

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Objectives Mammalian palatogenesis is a highly regulated morphogenetic process to form the intact roof of the oral cavity. Long noncoding RNAs (lncRNAs) and mRNAs participate in numerous biological and pathological processes, but their roles in palatal development and causing orofacial clefts (OFC) remain to be clarified. Methods Palatal tissues were separated from ICR mouse embryos at four stages (E10.5, E13.5, E15, and E17). Then, RNA sequencing (RNA‐seq) was used. Various analyses were performed to explore the results. Finally, hub genes were validated via qPCR and in situ hybridization. Results Starting from E10.5, the expression of cell adhesion genes escalated in the following stages. Cilium assembly and ossification genes were both upregulated at E15 compared with E13.5. Besides, the expression of cilium assembly genes was also increased at E17 compared with E15. Expression patterns of three lncRNAs (H19, Malat1, and Miat) and four mRNAs (Cdh1, Irf6, Grhl3, Efnb1) detected in RNA‐seq were validated. Conclusions This study provides a time‐series expression landscape of mRNAs and lncRNAs during palatogenesis, which highlights the importance of processes such as cell adhesion and ossification. Our results will facilitate a deeper understanding of the complexity of gene expression and regulation during palatogenesis.

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Section: Resultsmentioning

confidence: 99%

Time‐series expression profiles of mRNAs and lncRNAs during mammalian palatogenesis

Huang

Zhong

et al. 2022

Oral Diseases

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“…32,33 The atRA-exposed palate shelves failed to elevate in our study. Despite extensive research on atRA-induced cleft palate, 8,[34][35][36] long-term effects of atRA exposure have rarely been reported. Single-cell transcriptome technology has never been used to reveal the single-cell landscape of cleft palate and the role of immune cells has been ignored as well.…”

Section: Discussionmentioning

confidence: 99%

“…However, atRA can induce multiple congenital defects, with cleft palate as one of the major malformations 7 . Previous studies on cleft palate mice have mainly focused on E13.5-14.5 8,9 . In this study, we examined mouse palate tissue of E16.5 to observe the long-term effects of atRA on the palate.…”

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confidence: 99%

Single-cell Transcriptomics Reveals Activation of Macrophages in All-trans Retinoic Acid (atRA)-induced Cleft Palate

Wang,

Xu,

Zhao

et al. 2023

Journal of Craniofacial Surgery

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Cleft palate is among the most common birth defects with an impact on swallowing and speaking and is difficult to diagnose with ultrasound during pregnancy. In this study, we systematically capture the cellular composition of all-trans retinoic acid (atRA)-exposed and normal embryonic gestation 16.5 days mouse palate by the single-cell RNA sequencing technique. The authors identified 14 major cell types with the largest proportion of fibroblasts. The proportion of myeloid cells in atRA-exposed palate was markedly higher than those in the normal palate tissue, especially M1-like macrophages and monocytes. The upregulated genes of the different expression genes between atRA-exposed palate and normal palate tissue were linked to the biological processes of leukocyte chemotaxis and migration. Protein TLR2, CXCR4, THBS1, MRC1, transcription factor encoding genes Cebpb, Fos, Jun, Rela, and signaling pathway IL-17 and phagosome were found to be significantly involved in these processes. Subsequently, cellular communication network analysis suggested that myeloid-centered cell interactions SELL, SELPLG, MIF, CXCL, ANNEXIN, THBS, and NECTIN were significantly more activated in atRA-exposed palate. Overall, we delineate the single-cell landscape of atRA-induced cleft palate, revealing the effects of overexposure to atRA during palate tissue development and providing insights for the diagnosis of cleft palate.

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“…MEPM cell migration and proliferation play significant roles in the formation of facial structures (He et al, 2008). Many studies have investigated whether atRA inhibits MEPM cell proliferation (Liu et al, 2016;Liu et al, 2021;Yoshioka et al, 2021;. However, the molecular mechanism by which HSL affects cell migration and proliferation needs to be fully clarified.…”

Section: Discussionmentioning

confidence: 99%

The involvement of hormone-sensitive lipase in all-trans retinoic acid induced cleft palate

Zheng¹,

Ye²

2022

Int. J. Dev. Biol.

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Abnormally high concentrations of all-trans retinoic acid (atRA) induce cleft palate, which is accompanied by abnormal migration and proliferation of mouse embryonic palatal mesenchyme (MEPM) cells. Hormone-sensitive lipase (HSL) is involved in many embryonic development processes. The current study was designed to elucidate the mechanism of HSL in cleft palate induced by atRA. To establish a cleft palate model in Kunming mice, pregnant mice were administered atRA (70 mg/kg) by gavage at embryonic Day 10.5 (E10.5). Embryonic palates were obtained through the dissection of pregnant mice at E15.5. Hematoxylin and eosin (H&E) staining was used to evaluate growth changes in the palatal shelves. The levels of HSL in MEPM cells were detected by immunohistochemistry, quantitative real-time reverse transcription-polymerase chain reaction (qRT‒PCR) and western blotting. RNAi was applied to construct vectors expressing HSL small interference RNAs (siRNAs). The vectors were transfected into MEPM cells. Cell proliferation and migration were evaluated by the cell counting kit-8 (CCK-8) assay and wound healing assay, respectively. The palatal shelves in the atRA group had separated at E15.5 without fusing. In MEPM cells, the expression of HSL was reversed after atRA treatment, which caused cleft palate in vivo. In the atRA group, the proliferation of HSL siRNA-transfected cells was remarkably promoted, and the migration rate significantly increased in the HSL siRNA-transfected MEPM cells. These results suggested that HSL may be involved in cleft palate induced by atRA and that atRA enhances HSL levels to inhibit embryonic palate growth.

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LncRNA Meg3-mediated regulation of the Smad pathway in atRA-induced cleft palate

Cited by 11 publications

References 39 publications

Time‐series expression profiles of mRNAs and lncRNAs during mammalian palatogenesis

Time‐series expression profiles of mRNAs and lncRNAs during mammalian palatogenesis

Single-cell Transcriptomics Reveals Activation of Macrophages in All-trans Retinoic Acid (atRA)-induced Cleft Palate

The involvement of hormone-sensitive lipase in all-trans retinoic acid induced cleft palate

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