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

被引：19

作者：

Burgess, Claire L. ^{[1
,2
,3
,4
]}

Huang, Jessie ^{[1
,2
,3
,4
]}

Bawa, Pushpinder S. ^{[1
,2
]}

Alysandratos, Konstantinos-Dionysios ^{[1
,2
,3
,4
]}

Minakin, Kasey ^{[1
,2
,3
,4
]}

Ayers, Lauren J. ^{[1
,2
,3
,4
]}

Morley, Michael P. ^{[5
]}

Babu, Apoorva ^{[5
]}

Villacorta-Martin, Carlos ^{[1
,2
]}

Yampolskaya, Maria ^{[6
]}

Hinds, Anne ^{[3
,4
]}

Thapa, Bibek R. ^{[1
,2
,3
,4
]}

Wang, Feiya ^{[1
,2
]}

Matschulat, Adeline ^{[3
,4
,7
]}

Mehta, Pankaj ^{[6
]}

Morrisey, Edward E. ^{[5
]}

Varelas, Xaralabos ^{[1
,2
,3
,4
,7
]}

Kotton, Darrell N. ^{[1
,2
,3
,4
]}

机构：

[1] Boston Univ, Ctr Regenerat Med, Boston, MA 02118 USA

[2] Boston Med Ctr, Boston, MA 02118 USA

[3] Boston Univ, Chobanian & Avedisian Sch Med, Pulm Ctr, Boston, MA 02118 USA

[4] Boston Univ, Chobanian & Avedisian Sch Med, Dept Med, Boston, MA 02118 USA

[5] Univ Penn, Perelman Sch Med, Penn CHOP Lung Biol Inst, Philadelphia, PA 19104 USA

[6] Boston Univ, Dept Phys, Boston, MA 02215 USA

[7] Boston Univ, Chobanian & Avedisian Sch Med, Dept Biochem & Cell Biol, Boston, MA 02118 USA

来源：

CELL STEM CELL | 2024年 / 31卷 / 05期

关键词：

PULMONARY-FIBROSIS; LUNG DEVELOPMENT; IPS CELLS; DIFFERENTIATION; TRANSDIFFERENTIATION; EXPRESSION; EXPOSURE; REGENERATION; PROGENITOR; REGULATORS;

D O I：

10.1016/j.stem.2024.03.017

中图分类号：

Q813 [细胞工程];

学科分类号：

摘要：

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.

引用

页码：657 / 675.e8

页数：28

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