Air-liquid interface culture promotes maturation and allows environmental exposure of pluripotent stem cell–derived alveolar epithelium

Type 2 alveolar epithelial cells (AT2s), facultative progenitor cells of the lung alveolus, play a vital role in the biology of the distal lung. In vitro model systems that incorporate human cells, recapitulate the biology of primary AT2s, and interface with the outside environment could serve as us...

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Main Authors: Abo, Kristine M, Sainz de Aja, Julio, Lindstrom-Vautrin, Jonathan, Alysandratos, Konstantinos-Dionysios, Richards, Alexsia, Garcia-de-Alba, Carolina, Huang, Jessie, Hix, Olivia T, Werder, Rhiannon B, Bullitt, Esther, Hinds, Anne, Falconer, Isaac, Villacorta-Martin, Carlos, Jaenisch, Rudolf, Kim, Carla F, Kotton, Darrell N, Wilson, Andrew A
Other Authors: Massachusetts Institute of Technology. Department of Biology
Format: Article
Language:English
Published: American Society for Clinical Investigation 2022
Online Access:https://hdl.handle.net/1721.1/146847
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author Abo, Kristine M
Sainz de Aja, Julio
Lindstrom-Vautrin, Jonathan
Alysandratos, Konstantinos-Dionysios
Richards, Alexsia
Garcia-de-Alba, Carolina
Huang, Jessie
Hix, Olivia T
Werder, Rhiannon B
Bullitt, Esther
Hinds, Anne
Falconer, Isaac
Villacorta-Martin, Carlos
Jaenisch, Rudolf
Kim, Carla F
Kotton, Darrell N
Wilson, Andrew A
author2 Massachusetts Institute of Technology. Department of Biology
author_facet Massachusetts Institute of Technology. Department of Biology
Abo, Kristine M
Sainz de Aja, Julio
Lindstrom-Vautrin, Jonathan
Alysandratos, Konstantinos-Dionysios
Richards, Alexsia
Garcia-de-Alba, Carolina
Huang, Jessie
Hix, Olivia T
Werder, Rhiannon B
Bullitt, Esther
Hinds, Anne
Falconer, Isaac
Villacorta-Martin, Carlos
Jaenisch, Rudolf
Kim, Carla F
Kotton, Darrell N
Wilson, Andrew A
author_sort Abo, Kristine M
collection MIT
description Type 2 alveolar epithelial cells (AT2s), facultative progenitor cells of the lung alveolus, play a vital role in the biology of the distal lung. In vitro model systems that incorporate human cells, recapitulate the biology of primary AT2s, and interface with the outside environment could serve as useful tools to elucidate functional characteristics of AT2s in homeostasis and disease. We and others recently adapted human induced pluripotent stem cell-derived AT2s (iAT2s) for air-liquid interface (ALI) culture. Here, we comprehensively characterize the effects of ALI culture on iAT2s and benchmark their transcriptional profile relative to both freshly sorted and cultured primary human fetal and adult AT2s. We find that iAT2s cultured at ALI maintain an AT2 phenotype while upregulating expression of transcripts associated with AT2 maturation. We then leverage this platform to assay the effects of exposure to clinically significant, inhaled toxicants including cigarette smoke and electronic cigarette vapor.
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spelling mit-1721.1/1468472022-12-13T03:40:06Z Air-liquid interface culture promotes maturation and allows environmental exposure of pluripotent stem cell–derived alveolar epithelium Abo, Kristine M Sainz de Aja, Julio Lindstrom-Vautrin, Jonathan Alysandratos, Konstantinos-Dionysios Richards, Alexsia Garcia-de-Alba, Carolina Huang, Jessie Hix, Olivia T Werder, Rhiannon B Bullitt, Esther Hinds, Anne Falconer, Isaac Villacorta-Martin, Carlos Jaenisch, Rudolf Kim, Carla F Kotton, Darrell N Wilson, Andrew A Massachusetts Institute of Technology. Department of Biology Type 2 alveolar epithelial cells (AT2s), facultative progenitor cells of the lung alveolus, play a vital role in the biology of the distal lung. In vitro model systems that incorporate human cells, recapitulate the biology of primary AT2s, and interface with the outside environment could serve as useful tools to elucidate functional characteristics of AT2s in homeostasis and disease. We and others recently adapted human induced pluripotent stem cell-derived AT2s (iAT2s) for air-liquid interface (ALI) culture. Here, we comprehensively characterize the effects of ALI culture on iAT2s and benchmark their transcriptional profile relative to both freshly sorted and cultured primary human fetal and adult AT2s. We find that iAT2s cultured at ALI maintain an AT2 phenotype while upregulating expression of transcripts associated with AT2 maturation. We then leverage this platform to assay the effects of exposure to clinically significant, inhaled toxicants including cigarette smoke and electronic cigarette vapor. 2022-12-12T18:36:42Z 2022-12-12T18:36:42Z 2022 2022-12-12T18:27:25Z Article http://purl.org/eprint/type/JournalArticle https://hdl.handle.net/1721.1/146847 Abo, Kristine M, Sainz de Aja, Julio, Lindstrom-Vautrin, Jonathan, Alysandratos, Konstantinos-Dionysios, Richards, Alexsia et al. 2022. "Air-liquid interface culture promotes maturation and allows environmental exposure of pluripotent stem cell–derived alveolar epithelium." JCI Insight, 7 (6). en 10.1172/JCI.INSIGHT.155589 JCI Insight Creative Commons Attribution 4.0 International license https://creativecommons.org/licenses/by/4.0/ application/pdf American Society for Clinical Investigation American Society for Clinical Investigation
spellingShingle Abo, Kristine M
Sainz de Aja, Julio
Lindstrom-Vautrin, Jonathan
Alysandratos, Konstantinos-Dionysios
Richards, Alexsia
Garcia-de-Alba, Carolina
Huang, Jessie
Hix, Olivia T
Werder, Rhiannon B
Bullitt, Esther
Hinds, Anne
Falconer, Isaac
Villacorta-Martin, Carlos
Jaenisch, Rudolf
Kim, Carla F
Kotton, Darrell N
Wilson, Andrew A
Air-liquid interface culture promotes maturation and allows environmental exposure of pluripotent stem cell–derived alveolar epithelium
title Air-liquid interface culture promotes maturation and allows environmental exposure of pluripotent stem cell–derived alveolar epithelium
title_full Air-liquid interface culture promotes maturation and allows environmental exposure of pluripotent stem cell–derived alveolar epithelium
title_fullStr Air-liquid interface culture promotes maturation and allows environmental exposure of pluripotent stem cell–derived alveolar epithelium
title_full_unstemmed Air-liquid interface culture promotes maturation and allows environmental exposure of pluripotent stem cell–derived alveolar epithelium
title_short Air-liquid interface culture promotes maturation and allows environmental exposure of pluripotent stem cell–derived alveolar epithelium
title_sort air liquid interface culture promotes maturation and allows environmental exposure of pluripotent stem cell derived alveolar epithelium
url https://hdl.handle.net/1721.1/146847
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