Nuclear receptor Nr5a2 promotes diverse connective tissue fates in the jaw.
Nuclear receptor Nr5a2 promotes diverse connective tissue fates in the jaw.
复制标题
DOI：
10.1016/j.devcel.2023.02.011
复制
发表时间：
2023-03
影响因子：
11.8
通讯作者：
Hung-Jhen Chen;Lindsey Barske;J. Talbot;Olivia M. Dinwoodie;Ryan R. Roberts;D'Juan T Farmer;C. Jimenez;Amy E. Merrill;A. Tucker;J. G. Crump
中科院分区：
文献类型：
--
作者：
Hung-Jhen Chen;Lindsey Barske;J. Talbot;Olivia M. Dinwoodie;Ryan R. Roberts;D'Juan T Farmer;C. Jimenez;Amy E. Merrill;A. Tucker;J. G. Crump
器官发育涉及以时空精度持续生产不同类型的细胞。在脊椎动物的颌骨中，神经嵴来源的祖细胞不仅产生骨骼组织，而且还产生后来形成的肌腱和唾液腺。在这里，我们确定了多能性因子Nr5a2作为必不可少的细胞命运的决定在下巴。在斑马鱼和小鼠中，我们观察到Nr5a2在下颌骨迁移后神经嵴衍生细胞亚群中的瞬时表达。在斑马鱼nr5a2突变体中，正常情况下形成肌腱的表达nr5a2的细胞会产生多余的下颌软骨。在小鼠中，神经嵴特异性Nr5a2缺失导致类似的颌骨和中耳骨骼和肌腱缺陷，以及唾液腺缺失。单细胞分析表明，Nr5a2，不同于其在多能性中的作用，促进了下颌特异性染色质的可及性和基因表达，这对肌腱和腺体的命运至关重要。因此，Nr5a2的再利用促进结缔组织命运以产生颌和中耳功能所需的全部衍生物库。
Organ development involves the sustained production of diverse cell types with spatiotemporal precision. In the vertebrate jaw, neural-crest-derived progenitors produce not only skeletal tissues but also later-forming tendons and salivary glands. Here we identify the pluripotency factor Nr5a2 as essential for cell-fate decisions in the jaw. In zebrafish and mice, we observe transient expression of Nr5a2 in a subset of mandibular postmigratory neural-crest-derived cells. In zebrafishnr5a2mutants,nr5a2-expressing cells that would normally form tendons generate excess jaw cartilage. In mice, neural-crest-specificNr5a2loss results in analogous skeletal and tendon defects in the jaw and middle ear, as well as salivary gland loss. Single-cell profiling shows that Nr5a2, distinct from its roles in pluripotency, promotes jaw-specific chromatin accessibility and gene expression that is essential for tendon and gland fates. Thus, repurposing of Nr5a2 promotes connective tissue fates to generate the full repertoire of derivatives required for jaw and middle ear function.