Hedgehog-responsive PDGFRa(+) fibroblasts maintain a unique pool of alveolar epithelial progenitor cells during alveologenesis

Feng Gao; Changgong Li; Soula Danopoulos; Denise Al Alam; Neil Peinado; Sha Webster; Zea Borok; GoleNaz Adeli Kohbodi; Saverio Bellusci; Parviz Minoo

Cell Reports (Apr 2022)

Hedgehog-responsive PDGFRa(+) fibroblasts maintain a unique pool of alveolar epithelial progenitor cells during alveologenesis

Feng Gao,
Changgong Li,
Soula Danopoulos,
Denise Al Alam,
Neil Peinado,
Sha Webster,
Zea Borok,
GoleNaz Adeli Kohbodi,
Saverio Bellusci,
Parviz Minoo

Affiliations

Feng Gao: Division of Neonatology, Department of Pediatrics, LAC+USC Medical Center and Childrens Hospital Los Angeles, Los Angeles, CA 90033, USA
Changgong Li: Division of Neonatology, Department of Pediatrics, LAC+USC Medical Center and Childrens Hospital Los Angeles, Los Angeles, CA 90033, USA
Soula Danopoulos: Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA 90502, USA
Denise Al Alam: Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA 90502, USA
Neil Peinado: Division of Neonatology, Department of Pediatrics, LAC+USC Medical Center and Childrens Hospital Los Angeles, Los Angeles, CA 90033, USA
Sha Webster: Division of Neonatology, Department of Pediatrics, LAC+USC Medical Center and Childrens Hospital Los Angeles, Los Angeles, CA 90033, USA
Zea Borok: Hastings Center for Pulmonary Research, Keck School of Medicine of University of Southern California, Los Angeles, CA 90033, USA; Division of Pulmonary, Critical Care and Sleep Medicine, University of California San Diego School of Medicine, San Diego, CA 92093, USA
GoleNaz Adeli Kohbodi: Division of Neonatology, Department of Pediatrics, LAC+USC Medical Center and Childrens Hospital Los Angeles, Los Angeles, CA 90033, USA
Saverio Bellusci: Division of Neonatology, Department of Pediatrics, LAC+USC Medical Center and Childrens Hospital Los Angeles, Los Angeles, CA 90033, USA; Universities of Giessen and Marburg Lung Center (UGMLC), Justus-Liebig-University Giessen, German Center for Lung Research (DZL), 35390 Giessen, Germany
Parviz Minoo: Division of Neonatology, Department of Pediatrics, LAC+USC Medical Center and Childrens Hospital Los Angeles, Los Angeles, CA 90033, USA; Hastings Center for Pulmonary Research, Keck School of Medicine of University of Southern California, Los Angeles, CA 90033, USA; Corresponding author

Journal volume & issue: Vol. 39, no. 1
p. 110608

Abstract

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Summary: The lung alveolus is lined with alveolar type 1 (AT1) and type 2 (AT2) epithelial cells. During alveologenesis, increasing demand associated with expanding alveolar numbers is met by proliferating progenitor AT2s (pAT2). Little information exists regarding the identity of this population and their niche microenvironment. We show that during alveologenesis, Hedgehog-responsive PDGFRa(+) progenitors (also known as SCMFs) are a source of secreted trophic molecules that maintain a unique pAT2 population. SCMFs are in turn maintained by TGFβ signaling. Compound inactivation of Alk5 TβR2 in SCMFs reduced their numbers and depleted the pAT2 pool without impacting differentiation of daughter cells. In lungs of preterm infants who died with bronchopulmonary dysplasia, PDGFRa is reduced and the number of proliferative AT2s is diminished, indicating that an evolutionarily conserved mechanism governs pAT2 behavior during alveologenesis. SCMFs are a transient cell population, active only during alveologenesis, making them a unique stage-specific niche mesodermal cell type in mammalian organs.

Published in Cell Reports

ISSN: 2211-1247 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Science: Biology (General)
Website: http://www.cell.com/cell-reports/home

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