美國(guó)波士頓大學(xué)Darrell N. Kotton團(tuán)隊(duì)利用多能干細(xì)胞制備了人肺泡上皮I型細(xì)胞（AT1s）。相關(guān)論文發(fā)表在2024年4月19日出版的《細(xì)胞-干細(xì)胞》雜志上。
研究人員通過定向誘導(dǎo)多能干細(xì)胞（iPSCs）分化，體外構(gòu)建了人AT1模型系統(tǒng)。研究人員利用原代成體AT1全轉(zhuǎn)錄組揭示了在這些細(xì)胞中富集的因子和調(diào)控途徑，如Hippo-LATS-YAP/TAZ轉(zhuǎn)導(dǎo)信號(hào)。接下來(lái)，研究人員制備了iPSC衍生的肺泡上皮II型細(xì)胞（AT2s），并發(fā)現(xiàn)核YAP信號(hào)足以促進(jìn)AT2基因向AT1基因的廣泛轉(zhuǎn)錄組轉(zhuǎn)變。
由此產(chǎn)生的細(xì)胞表現(xiàn)出與人AT1細(xì)胞相似的分子、形態(tài)和功能表型，包括能形成平坦的上皮屏障，產(chǎn)生特征性細(xì)胞外基質(zhì)分子和分泌配體的功能。該研究結(jié)果提供了人類肺泡上皮分化的體外模型以及潛在的人AT1來(lái)源途徑。
據(jù)介紹，AT1s是遠(yuǎn)端肺部氣體交換屏障的組成部分，一直以來(lái)，要分離或在細(xì)胞培養(yǎng)中維持這種細(xì)胞都很困難。
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.
來(lái)源：科學(xué)網(wǎng)
原標(biāo)題：多能干細(xì)胞可誘導(dǎo)分化人肺泡上皮I型細(xì)胞
作者：小柯機(jī)器人