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P63+/Krt5+ Distal Airway Stem Cells are Essential for Lung Regeneration

ABSTRACT: This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

ORGANISM(S): Mus musculus

SUBMITTER: Frank McKeon

PROVIDER: E-GEOD-60849 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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p63(+)Krt5(+) distal airway stem cells are essential for lung regeneration.

Zuo Wei W Zhang Ting T Wu Daniel Zheng'An DZ Guan Shou Ping SP Liew Audrey-Ann AA Yamamoto Yusuke Y Wang Xia X Lim Siew Joo SJ Vincent Matthew M Lessard Mark M Crum Christopher P CP Xian Wa W McKeon Frank F

Nature 20141112 7536

Lung diseases such as chronic obstructive pulmonary disease and pulmonary fibrosis involve the progressive and inexorable destruction of oxygen exchange surfaces and airways, and have emerged as a leading cause of death worldwide. Mitigating therapies, aside from impractical organ transplantation, remain limited and the possibility of regenerative medicine has lacked empirical support. However, it is clinically known that patients who survive sudden, massive loss of lung tissue from necrotizing ...[more]

PMID: 25383540

Similar Datasets

p63+/Krt5+ Distal Airway Stem Cells are Essential for Lung Regeneration (transplanted and damaged)

Project description:The possibility of lung regeneration has been long discounted due to the irreversible nature of chronic lung diseases. However, patients who sustain massive loss of lung tissue during acute infections often recover full pulmonary function. Correspondingly, we previously demonstrated lung regeneration in mice following H1N1 influenza virus infection and implicated p63+Krt5+ distal airway stem cells, or DASCp63/Krt5, in this process. We show here that rare, preexisting DASCp63/K5 undergo a proliferative expansion in response to influenza and lineage-trace to nascent alveoli assembled at sites of interstitial inflammation. We also show that the ablation of DASCp63/Krt5 in vivo prevents the regeneration of lung tissue following influenza leading to pre-fibrotic lesions and deficient oxygen exchange. Finally, we demonstrate that exogenously cloned and propagated DASCp63/Krt5 readily contribute to lung regeneration following transplantation. The transplanted DASC ameliorated influenza-induced lung injury. These data suggest that DASCp63/K5 are required for lung regeneration and may have therapeutic utility in acute and chronic lung diseases. Transplanted DASC cells incorporated into damaged host lung were laser capture microdissected and analyzed. Duplicate mice were included. We used the Affymetrix Mouse Exon 1.0 ST platform

2014-11-20 | E-GEOD-60830 | biostudies-arrayexpress

p63+/Krt5+ Distal Airway Stem Cells are Essential for Lung Regeneration (before and after in vitro differentiation)

Project description:The possibility of lung regeneration has been long discounted due to the irreversible nature of chronic lung diseases. However, patients who sustain massive loss of lung tissue during acute infections often recover full pulmonary function. Correspondingly, we previously demonstrated lung regeneration in mice following H1N1 influenza virus infection and implicated p63+Krt5+ distal airway stem cells, or DASCp63/Krt5, in this process. We show here that rare, preexisting DASCp63/K5 undergo a proliferative expansion in response to influenza and lineage-trace to nascent alveoli assembled at sites of interstitial inflammation. We also show that the ablation of DASCp63/Krt5 in vivo prevents the regeneration of lung tissue following influenza leading to pre-fibrotic lesions and deficient oxygen exchange. Finally, we demonstrate that exogenously cloned and propagated DASCp63/Krt5 readily contribute to lung regeneration following transplantation. The transplanted DASC ameliorated influenza-induced lung injury. These data suggest that DASCp63/K5 are required for lung regeneration and may have therapeutic utility in acute and chronic lung diseases. Stem cells before and after in vitro differentiation were subjected to whole genome microarray analysis. Duplicates were included for each sample. We used the Affymetrix Mouse Exon 1.0 ST platform

2014-11-20 | E-GEOD-60828 | biostudies-arrayexpress

Distal airway stem cells yield alveoli in vitro and during lung regeneration following H1N1 influenza infection

Project description:This SuperSeries is composed of the following subset Series: GSE32600: Distal airway stem cells yield alveoli in vitro and during lung regeneration following H1N1 influenza infection (colony) GSE32602: Distal airway stem cells yield alveoli in vitro and during lung regeneration following H1N1 influenza infection (LCM_Four populations of cells) GSE32604: Distal airway stem cells yield alveoli in vitro and during lung regeneration following H1N1 influenza infection (stem cell clones NESC,TASC,DASC) Refer to individual Series

2011-11-01 | E-GEOD-32606 | biostudies-arrayexpress

Distal airway stem cells yield alveoli in vitro and during lung regeneration following H1N1 influenza infection (colony)

Project description:The extent of lung regeneration following catastrophic damage and the potential role of adult stem cells in such a process remains obscure. Sublethal infection of mice with an H1N1 influenza virus related to that of the 1918 pandemic triggers massive airway damage followed by apparent regeneration. We show here that p63-expressing stem cells in the bronchiolar epithelium undergo rapid proliferation after infection and radiate to interbronchiolar regions of alveolar ablation. Once there, these cells assemble into discrete, Krt5+ pods and initiate expression of markers typical of alveoli. Gene expression profiles of these pods suggest that they are intermediates in the reconstitution of the alveolar-capillary network eradicated by viral infection. The dynamics of this p63-expressing stem cell in lung regeneration mirrors our parallel findings that defined pedigrees of human distal airway stem cells assemble alveoli-like structures in vitro and suggests new therapeutic avenues to acute and chronic airway disease. 3 colonies fron control and H1N1 influenza treated lungs (12 dpi) ,each were picked for whole genome microarray analysis

2011-11-01 | E-GEOD-32600 | biostudies-arrayexpress

p63+/Krt5+ Distal Airway Stem Cells are Essential for Lung Regeneration (Dtox treatment)

Project description:The possibility of lung regeneration has been long discounted due to the irreversible nature of chronic lung diseases. However, patients who sustain massive loss of lung tissue during acute infections often recover full pulmonary function. Correspondingly, we previously demonstrated lung regeneration in mice following H1N1 influenza virus infection and implicated p63+Krt5+ distal airway stem cells, or DASCp63/Krt5, in this process. We show here that rare, preexisting DASCp63/K5 undergo a proliferative expansion in response to influenza and lineage-trace to nascent alveoli assembled at sites of interstitial inflammation. We also show that the ablation of DASCp63/Krt5 in vivo prevents the regeneration of lung tissue following influenza leading to pre-fibrotic lesions and deficient oxygen exchange. Finally, we demonstrate that exogenously cloned and propagated DASCp63/Krt5 readily contribute to lung regeneration following transplantation. The transplanted DASC ameliorated influenza-induced lung injury. These data suggest that DASCp63/K5 are required for lung regeneration and may have therapeutic utility in acute and chronic lung diseases. DASC stem cells were ablated by Dtox treatment in Krt6:DTR mouse model. Control and stem cell ablated lungs were analyzed. We used the Affymetrix Mouse Exon 1.0 ST platform

2014-11-20 | E-GEOD-60829 | biostudies-arrayexpress

Expression data from epigenetic memory and preferential lineage-specific differentiation in induced pluripotent stem cells derived from human pancreatic islet beta cells

Project description:Three induced pluripotent stem (iPS) cell lines were generated from pancreatic BCD (beta-cell-derived cells). One iPS cell clone was derived from pancreatic non-beta cells. We used microarrays to study the gene expression profiles of beta-iPSCs, and compared the expression of genes in their somatic parental cells and other ES and iPS cells. All BiPSC lines were tested in pluripotency assays (including morphology, immunostainings and qRT-PCR) for known pluripotency markers, as well as differentiation capacity in vivo and in vitro.

2011-07-31 | E-GEOD-29880 | biostudies-arrayexpress

Expression data from parthenogenetic and WT iPS samples and their parental fibroblasts

Project description:Three parthenogenetic induced pluripotent stem cell (PgHiPSCs) lines were generated from each of the ovarian teratoma cell lines (two distinct individuals). Two normal iPS cell lines were generated from normal fibroblasts. Three biological replicates of normal embryonic stem cells (H9, HESCs) were perfomed. We used microarrays to study the gene expression profiles of the PgHiPSCs, and compared the expression of genes to both embryonic and induced pluripotent stem cell, to identify paternally expressed genes that are down-regulated in the PgHiPSC lines. All parthenogenetic and normal iPS cell lines, were tested for pluripotency assays (inclusing, morphology, immuno stanings and qRT-PCR for known pluripotency markers, differentiation capacity in vivo and in vitro)

2011-05-31 | E-GEOD-27362 | biostudies-arrayexpress

Expression data from WT and ELK-1 overexpressing stem cells

Project description:Two ELK-1 overexpressing cells were generated from CSES7 cell line and compared to WT CSES7. We used microarrays to study the gene expression profiles of the ELK-1 overexpressing cells in order to identify ELK-1 target genes that might be involve in the processes of apoptosis and differentiation CSES7 cells were transfected with the ELK-1 vector.

2013-07-12 | E-GEOD-48792 | biostudies-arrayexpress

Distal airway stem cells yield alveoli in vitro and during lung regeneration following H1N1 influenza infection (stem cell clones NESC,TASC,DASC)

Project description:The extent of lung regeneration following catastrophic damage and the potential role of adult stem cells in such a process remains obscure. Sublethal infection of mice with an H1N1 influenza virus related to that of the 1918 pandemic triggers massive airway damage followed by apparent regeneration. We show here that p63-expressing stem cells in the bronchiolar epithelium undergo rapid proliferation after infection and radiate to interbronchiolar regions of alveolar ablation. Once there, these cells assemble into discrete, Krt5+ pods and initiate expression of markers typical of alveoli. Gene expression profiles of these pods suggest that they are intermediates in the reconstitution of the alveolar-capillary network eradicated by viral infection. The dynamics of this p63-expressing stem cell in lung regeneration mirrors our parallel findings that defined pedigrees of human distal airway stem cells assemble alveoli-like structures in vitro and suggests new therapeutic avenues to acute and chronic airway disease. The long-term self-renewal potential of the putative human stem cell clones (NESC,TASC,DASC) allowed us to isolate independent pedigrees for the analysis of the progeny of a single cell. Expansion of these lines yielded abundant immature cells of known pedigree for a range of differentiation assays to assess lineage potential. All stem cells were grown on feeder layer (3T3).NESC were differentiated using Air liquid interface system (ALI), 3D matrigel system (MAT) and Self assembling sphere culture(SAS). The differentiation potential of TASC and DASC were studied using ALI and MAT systems.

2011-11-01 | E-GEOD-32604 | biostudies-arrayexpress

Expression data from undifferentiated human induced pluripotent stem cells

Project description:Expression data from undifferentiated human induced pluripotent stem cells total RNA was isolated from undifferentiated induced pluripotent stem cells grown in standard HESC growth conditions on mouse embryonic fibroblast feeder layer.

2010-04-09 | E-GEOD-21243 | biostudies-arrayexpress

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