美国波士顿大学Darrell N. Kotton团队利用多能干细胞制备了人肺泡上皮I型细胞（AT1s）。相关论文发表在2024年4月19日出版的《细胞-干细胞》杂志上。

研究人员通过定向诱导多能干细胞（iPSCs）分化，体外构建了人AT1模型系统。研究人员利用原代成体AT1全转录组揭示了在这些细胞中富集的因子和调控途径，如Hippo-LATS-YAP/TAZ转导信号。接下来，研究人员制备了iPSC衍生的肺泡上皮II型细胞（AT2s），并发现核YAP信号足以促进AT2基因向AT1基因的广泛转录组转变。

由此产生的细胞表现出与人AT1细胞相似的分子、形态和功能表型，包括能形成平坦的上皮屏障，产生特征性细胞外基质分子和分泌配体的功能。该研究结果提供了人类肺泡上皮分化的体外模型以及潜在的人AT1来源途径。

据介绍，AT1s是远端肺部气体交换屏障的组成部分，一直以来，要分离或在细胞培养中维持这种细胞都很困难。

附：英文原文

Title: Generation of human alveolar epithelial type I cells from pluripotent stem cells

Author: Claire L. Burgess, Jessie Huang, Pushpinder S. Bawa, Konstantinos-Dionysios Alysandratos, Kasey Minakin, Lauren J. Ayers, Michael P. Morley, Apoorva Babu, Carlos Villacorta-Martin, Maria Yampolskaya, Anne Hinds, Bibek R. Thapa, Feiya Wang, Adeline Matschulat, Pankaj Mehta, Edward E. Morrisey, Xaralabos Varelas, Darrell N. Kotton

Issue&Volume: 2024-04-19

Abstract: Alveolar epithelial type I cells (AT1s) line the gas exchange barrier of the distal lung and have been historically challenging to isolate or maintain in cell culture. Here, we engineer a human in vitro AT1 model system via directed differentiation of induced pluripotent stem cells (iPSCs). We use primary adult AT1 global transcriptomes to suggest benchmarks and pathways, such as Hippo-LATS-YAP/TAZ signaling, enriched in these cells. Next, we generate iPSC-derived alveolar epithelial type II cells (AT2s) and find that nuclear YAP signaling is sufficient to promote a broad transcriptomic shift from AT2 to AT1 gene programs. The resulting cells express a molecular, morphologic, and functional phenotype reminiscent of human AT1 cells, including the capacity to form a flat epithelial barrier producing characteristic extracellular matrix molecules and secreted ligands. Our results provide an in vitro model of human alveolar epithelial differentiation and a potential source of human AT1s.

DOI: 10.1016/j.stem.2024.03.017

Source: https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(24)00098-5