Regeneration of the human segmentation clock in somitoids in vitro-猫眼课题宝

DOI：

10.15252/embj.2022110928

发表时间：

2022-10

期刊：

The EMBO Journal

影响因子：

通讯作者：

中科院分区：

其他

文献类型：

作者：

Yue Qin;Xingnan Huang;Zepo Cai;Baomei Cai;Jiangping He;Yuxiang Yao;Chunhua Zhou;J. Kuang;Yihang Yang;Huan Chen;Yating Chen;Sihua Ou;Lijun Chen;Fang Wu;Ning Guo;Yapei Yuan;Xiangyu Zhang;Wei Pang;Ziyu Feng;Shengyong Yu;Jing Liu;Shangtao Cao;D. Pei

每个脊椎动物物种似乎都有一个独特的定时机制，用于沿着脊柱沿着形成体节，由于技术和伦理的限制，人类的过程在分子水平上仍然知之甚少。在这里，我们报告的重建人类分割时钟直接重编程。我们首先将人尿上皮细胞重编程为能够长期自我更新和形成具有前后轴的体节样体的前体中胚层（PSM）状态。通过将RNA报告基因Pepper插入这些iPSM细胞的HES 7和MESP 2位点，我们表明这两种转录物在产生的体节样体中以约5小时/周期振荡。GFP标记的内源性HES 7蛋白在体节形成期间沿沿着前后轴移动。地理测序分析进一步证实了前后极性，并揭示了WNT、BMP、FGF和RA信号分子以及HOXA-D家族成员的局部表达。我们的研究证明了从体细胞直接重建人类分割时钟，这可能允许未来解剖这种时钟的机制和组成部分，并有助于再生医学。

Each vertebrate species appears to have a unique timing mechanism for forming somites along the vertebral column, and the process in human remains poorly understood at the molecular level due to technical and ethical limitations. Here, we report the reconstitution of human segmentation clock by direct reprogramming. We first reprogrammed human urine epithelial cells to a presomitic mesoderm (PSM) state capable of long‐term self‐renewal and formation of somitoids with an anterior‐to‐posterior axis. By inserting the RNA reporter Pepper into HES7 and MESP2 loci of these iPSM cells, we show that both transcripts oscillate in the resulting somitoids at ~5 h/cycle. GFP‐tagged endogenous HES7 protein moves along the anterior‐to‐posterior axis during somitoid formation. The geo‐sequencing analysis further confirmed anterior‐to‐posterior polarity and revealed the localized expression of WNT, BMP, FGF, and RA signaling molecules and HOXA‐D family members. Our study demonstrates the direct reconstitution of human segmentation clock from somatic cells, which may allow future dissection of the mechanism and components of such a clock and aid regenerative medicine.

Regeneration of the human segmentation clock in somitoids in vitro

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