海南医学院马燕琳等研究人员合作发现，单细胞RNA测序揭示人类肺部在胚胎阶段近端-远端模式的发育程序。相关论文于2023年4月21日在线发表在《细胞研究》杂志上。

研究人员使用单细胞RNA测序调查了人类胚胎受精后第4-8周（卡内基分期12-21）的早期肺部发育，并获得了169686个细胞的转录组图谱。研究人员观察到近端和远端上皮细胞在第4周，即肺器官形成开始时的可辨认的基因表达模式。此外，研究人员确定了近端（如THRB和EGR3）和远端（如ETV1和SOX6）上皮细胞模式的新型转录调节因子。进一步剖析发现各种基质细胞群，包括早期胚胎期的BDNF⁺群体，这提供了具有空间特异性的近端-远端模式化的微环境。此外，研究人员阐明了在肺部发育的早期阶段，气道和血管平滑肌祖细胞的细胞命运分叉和成熟。

总之，这项研究扩大了人类肺部发育生物学在早期胚胎阶段的范围。内在的转录调节因子和新的微环境提供者的发现，加深了对人类肺部发育中上皮近端-远端模式的理解，并为再生医学开辟了新的途径。

据介绍，肺是人类的主要呼吸器官，其中近端气道和远端肺泡分别负责空气传导和气体交换。然而，在人类肺部发育的胚胎阶段，近端-远端模式的调节在很大程度上是未知的。

附：英文原文

Title: Single-cell RNA sequencing reveals the developmental program underlying proximal–distal patterning of the human lung at the embryonic stage

Author: Cao, Shangtao, Feng, Huijian, Yi, Hongyan, Pan, Mengjie, Lin, Lihui, Zhang, Yao Santo, Feng, Ziyu, Liang, Weifang, Cai, Baomei, Li, Qi, Xiong, Zhi, Shen, Qingmei, Ke, Minjing, Zhao, Xing, Chen, Huilin, He, Qina, Min, Mingwei, Cai, Quanyou, Liu, He, Wang, Jie, Pei, Duanqing, Chen, Jiekai, Ma, Yanlin

Issue&Volume: 2023-04-21

Abstract: The lung is the primary respiratory organ in human, in which the proximal airway and the distal alveoli are responsible for air conduction and gas exchange, respectively. However, the regulation of proximal–distal patterning at the embryonic stage of human lung development is largely unknown. Here we investigated the early lung development of human embryos at weeks 4–8 post fertilization (Carnegie stages 12–21) using single-cell RNA sequencing, and obtained a transcriptomic atlas of 169,686 cells. We observed discernible gene expression patterns of proximal and distal epithelia at week 4, upon the initiation of lung organogenesis. Moreover, we identified novel transcriptional regulators of the patterning of proximal (e.g., THRB and EGR3) and distal (e.g., ETV1 and SOX6) epithelia. Further dissection revealed various stromal cell populations, including an early-embryonic BDNF+ population, providing a proximal–distal patterning niche with spatial specificity. In addition, we elucidated the cell fate bifurcation and maturation of airway and vascular smooth muscle progenitor cells at the early stage of lung development. Together, our study expands the scope of human lung developmental biology at early embryonic stages. The discovery of intrinsic transcriptional regulators and novel niche providers deepens the understanding of epithelial proximal–distal patterning in human lung development, opening up new avenues for regenerative medicine.

DOI: 10.1038/s41422-023-00802-6

Source: https://www.nature.com/articles/s41422-023-00802-6