Faculty of Life Sciences and Medicine, School of Life Science and Technology, Harbin Institute of Technology, Harbin 150001, China.
State Key Laboratory of Urban Water Resource and Environment, Harbin Institute of Technology, Harbin 150001, China.
Int J Mol Sci. 2024 Jul 26;25(15):8184. doi: 10.3390/ijms25158184.
The domain is important for normal embryonic growth and development. The heart is the earliest developing and functioning organ of the embryo. In this study, we constructed a transcriptional termination model by inserting termination sequences and clarified that the lack of long non-coding RNA (lncRNA) expression in the domain caused the death of maternal insertion mutant (MKI) and homozygous mutant (HOMO) mice starting from E13.5. Parental insertion mutants (PKI) can be born and grow normally. Macroscopically, dying MKI and HOMO embryos showed phenomena such as embryonic edema and reduced heart rate. Hematoxylin and eosin (H.E.) staining showed thinning of the myocardium in MKI and HOMO embryos. In situ hybridization (IHC) and quantitative reverse-transcription polymerase chain reaction (qRT-PCR) showed downregulation of lnc, , and expression in MKI and HOMO hearts. The results of single-cell RNA sequencing (scRNA-Seq) analysis indicated that the lack of lncRNA expression in the domain led to reduced proliferation of epicardial cells and may be an important cause of cardiac dysplasia. In conclusion, this study demonstrates that domain lncRNAs play an integral role in ventricular development.
该结构域对于正常胚胎生长和发育很重要。心脏是胚胎最早发育和起作用的器官。在这项研究中，我们构建了一个转录终止模型，通过插入终止序列，阐明缺失 结构域的长非编码 RNA（lncRNA）表达导致母源插入突变体（MKI）和纯合突变体（HOMO）小鼠从 E13.5 开始死亡。父源插入突变体（PKI）可以出生并正常生长。大体上，死亡的 MKI 和 HOMO 胚胎表现出胚胎水肿和心率降低等现象。苏木精和伊红（H.E.）染色显示 MKI 和 HOMO 胚胎的心肌变薄。原位杂交（IHC）和定量逆转录聚合酶链反应（qRT-PCR）显示 MKI 和 HOMO 心脏中的 lncRNA、和表达下调。单细胞 RNA 测序（scRNA-Seq）分析的结果表明， 结构域中 lncRNA 的缺失导致心外膜细胞增殖减少，可能是心脏发育不良的重要原因。总之，这项研究表明 结构域 lncRNAs 对心室发育起着不可或缺的作用。
