title: Rare SOX2+Airway Progenitor Cells Generate KRT5+Cells that Repopulate Damaged Alveolar Parenchyma following Influenza Virus Infection.
abstract: Recent studies have implicated keratin 5 (KRT5)+cells in repopulation of damaged lung tissue following severe H1N1 influenza virus infection. However, the origins of the cells repopulating the injured alveolar region remain controversial. We sought to determine the cellular dynamics of lung repair following influenza infection and define whether nascent KRT5+cells repopulating alveolar epithelium were derived from pre-existing alveolar or airway progenitor cells. We found that the wound-healing response begins with proliferation of SOX2+SCGB1A1-KRT5-progenitor cells in airways. These cells generate nascent KRT5+cells as an early response to airway injury and yield progeny that colonize damaged alveolar parenchyma. Moreover, we show that local alveolar progenitors do not contribute to nascent KRT5+cells after injury. Repopulation of injured airway and alveolar regions leads to proximalization of distal airways by pseudostratified epithelium and of alveoli by airway-derived epithelial cells that lack the normal characteristics of mature airway or alveolar epithelium.
authors: Lung and Regenerative Medicine Institutes, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
authors: Samriddha
authors: S
authors: Ray
authors: Lung and Regenerative Medicine Institutes, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
authors: Norika
authors: N
authors: Chiba
authors: Lung and Regenerative Medicine Institutes, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
authors: Changfu
authors: C
authors: Yao
authors: Lung and Regenerative Medicine Institutes, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
authors: Xiangrong
authors: X
authors: Guan
authors: Lung and Regenerative Medicine Institutes, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA; Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA.
authors: Alicia M
authors: AM
authors: McConnell
authors: Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA.
authors: Brian
authors: B
authors: Brockway
authors: Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA.
authors: Loretta
authors: L
authors: Que
authors: Lung and Regenerative Medicine Institutes, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
authors: Jonathan L
authors: JL
authors: McQualter
authors: Lung and Regenerative Medicine Institutes, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA; Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA. Electronic address: barry.stripp@cshs.org.
authors: Barry R
authors: BR
authors: Stripp
mesh_terms: D056809:Alveolar Epithelial Cells / Q000166:cytology / Q000378:metabolism* / Q000821:virology; D000818:Animals; D015415:Biomarkers; D002454:Cell Differentiation; D019070:Cell Lineage; D000066673:Cell Self Renewal / Q000235:genetics; D053118:Influenza A Virus, H1N1 Subtype; D053555:Keratin-5 / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D008954:Models, Biological; D009976:Orthomyxoviridae Infections / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000821:virology; D020545:Respiratory Mucosa / Q000166:cytology* / Q000378:metabolism* / Q000821:virology; D055748:SOXB1 Transcription Factors / Q000235:genetics / Q000378:metabolism*; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D053555:Keratin-5; D055748:SOXB1 Transcription Factors
keywords: SCGB1A1 lineage; SOX2 lineage; influenza virus; keratin 5; lung injury; lung repair; progenitor cells; wound repair