PMID- 26545903 OWN - NLM STAT- MEDLINE DCOM- 20160603 LR - 20200930 IS - 1522-1504 (Electronic) IS - 1040-0605 (Print) IS - 1040-0605 (Linking) VI - 310 IP - 2 DP - 2016 Jan 15 TI - Combinations of differentiation markers distinguish subpopulations of alveolar epithelial cells in adult lung. PG - L114-20 LID - 10.1152/ajplung.00337.2015 [doi] AB - Distal lung epithelium is maintained by proliferation of alveolar type II (AT2) cells and, for some daughter AT2 cells, transdifferentiation into alveolar type I (AT1) cells. We investigated if subpopulations of alveolar epithelial cells (AEC) exist that represent various stages in transdifferentiation from AT2 to AT1 cell phenotypes in normal adult lung and if they can be identified using combinations of cell-specific markers. Immunofluorescence microscopy showed that, in distal rat and mouse lungs, approximately 20-30% of NKX2.1(+) (or thyroid transcription factor 1(+)) cells did not colocalize with pro-surfactant protein C (pro-SP-C), a highly specific AT2 cell marker. In distal rat lung, NKX2.1(+) cells coexpressed either pro-SP-C or the AT1 cell marker homeodomain only protein x (HOPX). Not all HOPX(+) cells colocalize with the AT1 cell marker aquaporin 5 (AQP5), and some AQP5(+) cells were NKX2.1(+). HOPX was expressed earlier than AQP5 during transdifferentiation in rat AEC primary culture, with robust expression of both by day 7. We speculate that NKX2.1 and pro-SP-C colocalize in AT2 cells, NKX2.1 and HOPX or AQP5 colocalize in intermediate or transitional cells, and HOPX and AQP5 are expressed without NKX2.1 in AT1 cells. These findings suggest marked heterogeneity among cells previously identified as exclusively AT1 or AT2 cells, implying the presence of subpopulations of intermediate or transitional AEC in normal adult lung. CI - Copyright (c) 2016 the American Physiological Society. FAU - Liebler, Janice M AU - Liebler JM AUID- ORCID: 0000-0002-4166-6197 AD - Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, Will Rogers Institute Pulmonary Research Center, Keck School of Medicine, University of Southern California, Los Angeles, California; FAU - Marconett, Crystal N AU - Marconett CN AD - Department of Surgery, Keck School of Medicine, University of Southern California, Los Angeles, California; Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, California; Department of Biochemistry and Molecular Biology, Keck School of Medicine, University of Southern California, Los Angeles, California; and. FAU - Juul, Nicholas AU - Juul N AD - Department of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California; FAU - Wang, Hongjun AU - Wang H AD - Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, Will Rogers Institute Pulmonary Research Center, Keck School of Medicine, University of Southern California, Los Angeles, California; FAU - Liu, Yixin AU - Liu Y AD - Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, Will Rogers Institute Pulmonary Research Center, Keck School of Medicine, University of Southern California, Los Angeles, California; FAU - Flodby, Per AU - Flodby P AD - Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, Will Rogers Institute Pulmonary Research Center, Keck School of Medicine, University of Southern California, Los Angeles, California; FAU - Laird-Offringa, Ite A AU - Laird-Offringa IA AD - Department of Surgery, Keck School of Medicine, University of Southern California, Los Angeles, California; Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, California; Department of Biochemistry and Molecular Biology, Keck School of Medicine, University of Southern California, Los Angeles, California; and. FAU - Minoo, Parviz AU - Minoo P AD - Division of Newborn Medicine, Department of Pediatrics, and Children's Hospital Los Angeles, Keck School of Medicine, University of Southern California, Los Angeles, California. FAU - Zhou, Beiyun AU - Zhou B AD - Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, Will Rogers Institute Pulmonary Research Center, Keck School of Medicine, University of Southern California, Los Angeles, California; Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, California; bzhou@usc.edu. LA - eng GR - R01 HL114959/HL/NHLBI NIH HHS/United States GR - R01 HL122764/HL/NHLBI NIH HHS/United States GR - P30-DK-048522/DK/NIDDK NIH HHS/United States GR - HL-114094/HL/NHLBI NIH HHS/United States GR - R01 HL114094/HL/NHLBI NIH HHS/United States GR - HL-114959/HL/NHLBI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20151106 PL - United States TA - Am J Physiol Lung Cell Mol Physiol JT - American journal of physiology. Lung cellular and molecular physiology JID - 100901229 RN - 0 (Antigens, Differentiation) SB - IM MH - Aging MH - Alveolar Epithelial Cells/*cytology MH - Animals MH - Antigens, Differentiation/*metabolism MH - Cell Differentiation/physiology MH - Cell Transdifferentiation/*physiology MH - Cells, Cultured MH - Epithelial Cells/*cytology/metabolism MH - Mice MH - Pulmonary Alveoli/*cytology MH - Rats PMC - PMC4719049 OTO - NOTNLM OT - NKX2.1 OT - alveolar epithelial type I cell OT - alveolar epithelial type II cell OT - aquaporin-5 OT - homeodomain only protein x OT - intermediate cells OT - transdifferentiation EDAT- 2015/11/08 06:00 MHDA- 2016/06/04 06:00 PMCR- 2017/01/15 CRDT- 2015/11/08 06:00 PHST- 2015/09/23 00:00 [received] PHST- 2015/11/02 00:00 [accepted] PHST- 2015/11/08 06:00 [entrez] PHST- 2015/11/08 06:00 [pubmed] PHST- 2016/06/04 06:00 [medline] PHST- 2017/01/15 00:00 [pmc-release] AID - ajplung.00337.2015 [pii] AID - L-00337-2015 [pii] AID - 10.1152/ajplung.00337.2015 [doi] PST - ppublish SO - Am J Physiol Lung Cell Mol Physiol. 2016 Jan 15;310(2):L114-20. doi: 10.1152/ajplung.00337.2015. Epub 2015 Nov 6.