Differentiation of Human Pluripotent Stem Cells into Functional Lung Alveolar Epithelial Cells

被引：379

作者：

Jacob, Anjali ^{[1
,2
,3
,4
]}

Morley, Michael ^{[5
]}

Hawkins, Finn ^{[1
,2
,3
,4
]}

McCauley, Katherine B. ^{[1
,2
,3
,4
]}

Jean, J. C. ^{[1
,2
,3
,4
]}

Heins, Hillary ^{[6
]}

Na, Cheng-Lun ^{[8
]}

Weaver, Timothy E. ^{[8
]}

Vedaie, Marall ^{[1
,2
,3
,4
]}

Hurley, Killian ^{[1
,2
,3
,4
]}

Hinds, Anne ^{[3
,4
]}

Russo, Scott J. ^{[5
]}

Kook, Seunghyi ^{[7
]}

Zacharias, William ^{[5
]}

Ochs, Matthias ^{[9
]}

Traber, Katrina ^{[3
,4
]}

Quinton, Lee J. ^{[3
,4
]}

Crane, Ana ^{[10
]}

Davis, Brian R. ^{[10
]}

White, Frances V. ^{[6
]}

Wambach, Jennifer ^{[6
]}

Whitsett, Jeffrey A. ^{[8
]}

Cole, F. Sessions ^{[6
]}

Morrisey, Edward E. ^{[5
]}

Guttentag, Susan H. ^{[7
]}

Beers, Michael F. ^{[5
]}

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, Sch Med, Ctr Pulm, Boston, MA 02118 USA

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

[5] Univ Penn, Penn Ctr Pulm Biol, Philadelphia, PA 19104 USA

[6] Washington Univ, Sch Med, Edward Mallinckrodt Dept Pediat, St Louis, MO 63110 USA

[7] Vanderbilt Univ, Dept Pediat, Monroe Carell Jr Childrens Hosp, Nashville, TN 37232 USA

[8] Cincinnati Childrens Hosp Med Ctr, Div Pulm Biol, Cincinnati, OH 45229 USA

[9] Hannover Med Sch, Biomed Res Endstage & Obstruct Lung Dis Hannover, REBIRTH Cluster Excellence, Inst Funct & Appl Anat,German Ctr Lung Res DZL, D-30625 Hannover, Germany

[10] Univ Texas Hlth Sci Ctr Houston, Brown Fdn, Inst Mol Med, Ctr Stem Cell & Regenerat Med, Houston, TX 77030 USA

来源：

CELL STEM CELL | 2017年 / 21卷 / 04期

关键词：

SURFACTANT PROTEIN-B; II CELLS; IN-VITRO; RAT LUNG; SP-C; RESPIRATORY EPITHELIUM; GENE; FETAL; LOCALIZATION; EXPRESSION;

D O I：

10.1016/j.stem.2017.08.014

中图分类号：

Q813 [细胞工程];

学科分类号：

摘要：

Lung alveoli, which are unique to air-breathing organisms, have been challenging to generate from pluripotent stem cells (PSCs) in part because there are limited model systems available to provide the necessary developmental roadmaps for in vitro differentiation. Here we report the generation of alveolar epithelial type 2 cells (AEC2s), the facultative progenitors of lung alveoli, from human PSCs. Using multicolored fluorescent reporter lines, we track and purify human SFTPC+ alveolar progenitors as they emerge from endodermal precursors in response to stimulation of Wnt and FGF signaling. Purified PSCderived SFTPC+ cells form monolayered epithelial "alveolospheres'' in 3D cultures without the need for mesenchymal support, exhibit self-renewal capacity, and display additional AEC2 functional capacities. Footprint-free CRISPR-based gene correction of PSCs derived from patients carrying a homozygous surfactant mutation (SFTPB121ins2) restores surfactant processing in AEC2s. Thus, PSC-derived AEC2s provide a platform for disease modeling and future functional regeneration of the distal lung.

引用

页码：472 / +

页数：27

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