Department of Genomic Medicine, Seoul National University Hospital, Seoul, Republic of Korea.
Department of Pediatrics, Seoul National University College of Medicine, Seoul National University Children's Hospital, Seoul, Republic of Korea.
Childs Nerv Syst. 2022 Nov;38(11):2101-2111. doi: 10.1007/s00381-022-05675-5. Epub 2022 Oct 1.
The caudal cell mass (CCM) is an aggregate of undifferentiated pluripotent cells and the main player in secondary neurulation. Previous studies have elucidated the dynamic fate of the multipotent cell lineages, with a recent interest in the neuromesodermal progenitors. However, a transcriptomic analysis of the CCM during secondary neurulation has not been performed yet.
We analyzed RNA sequencing data of CCM samples at three different developmental stages of chicken embryos; HH16 (largest CCM phase), HH20 (secondary neural tube formation phase), and HH28 (degeneration phase).
The transcriptomic profiles were clearly distinguishable according to developmental stage, and HH20 was shown to have not only intermediate, but also unique properties in secondary neurulation. A total of 10,666 differentially expressed genes, including FGF18 and GDF11, were identified and enriched in several gene ontologies related to embryogenesis or organogenesis. We also found that genes encoding transcription factors, such as TWIST2, IRX4, HOXB4, HOXD13, LIN28A, CDX4, and Brachyury, were among the top-ranked differentially expressed genes.
Through transcriptomic profiling, we provided a picture of the developmental process of the CCM. We identified several key molecules or pathways involved in secondary neurulation and the pathogenesis of related diseases.
尾细胞群(CCM)是未分化多能细胞的集合体,是次级神经管形成的主要参与者。先前的研究已经阐明了多能细胞谱系的动态命运,最近人们对神经中胚层祖细胞产生了兴趣。然而,目前尚未对次级神经管形成过程中的 CCM 进行转录组分析。
我们分析了来自鸡胚三个不同发育阶段(HH16[最大 CCM 阶段]、HH20[次级神经管形成阶段]和 HH28[退化阶段])的 CCM 样本的 RNA 测序数据。
根据发育阶段,转录组图谱明显可区分,并且 HH20 不仅具有中间特性,而且在次级神经管形成中具有独特的特性。总共鉴定到 10666 个差异表达基因,包括 FGF18 和 GDF11,并在与胚胎发生或器官发生相关的几个基因本体论中富集。我们还发现,编码转录因子的基因,如 TWIST2、IRX4、HOXB4、HOXD13、LIN28A、CDX4 和 Brachyury,是差异表达基因中排名最高的基因之一。
通过转录组谱分析,我们提供了 CCM 发育过程的图片。我们确定了几个涉及次级神经管形成和相关疾病发病机制的关键分子或途径。