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Alveolar epithelial progenitor

Per Flodby, Janice Marie Liebler, Mitsuhiro Sunohara, Dan Ran, Alicia M McConnell, Manda Sai Krishnaveni, Agnes Banfalvi, Min Li, Barry R Stripp, Beiyun Zhou, Edward D Crandall, Parviz Minoo, Zea Borok
Previous studies have demonstrated resistance to naphthalene-induced injury in proximal airways of mice with lung epithelial-specific deletion of the tumor-suppressor gene Pten, attributed to increased proliferation of airway progenitors. We tested effects of Pten loss following bleomycin injury, a model typically used to study distal lung epithelial injury, in conditional PtenSFTPC-cre knockout mice. Pten-deficient airway epithelium exhibited marked hyperplasia, particularly in small bronchioles and at bronchoalveolar duct junctions, with reduced E-cadherin and β-catenin expression between cells towards the luminal aspect of the hyperplastic epithelium...
November 18, 2016: American Journal of Physiology. Lung Cellular and Molecular Physiology
Andrew Trecartin, Soula Danopoulos, Ryan Spurrier, Hanaa Knaneh-Monem, Michael Hiatt, Barbara Driscoll, Christian Hochstim, Denise Al-Alam, Tracy C Grikscheit
The cellular and molecular mechanisms that underpin regeneration of the human lung are unknown, and the study of lung repair has been impeded by the necessity for reductionist models that may exclude key components. We hypothesized that multicellular epithelial and mesenchymal cell clusters or lung organoid units (LuOU) could be transplanted to recapitulate proximal and distal cellular structures of the native lung and airways. Transplantation of LuOU resulted in the growth of tissue-engineered lung (TELu) that contained the necessary cell types consistent with native adult lung tissue and demonstrated proliferative cells at 2 and 4 weeks...
November 2016: Tissue Engineering. Part C, Methods
Samriddha Ray, Norika Chiba, Changfu Yao, Xiangrong Guan, Alicia M McConnell, Brian Brockway, Loretta Que, Jonathan L McQualter, Barry R Stripp
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...
November 8, 2016: Stem Cell Reports
Jiurong Liang, Yanli Zhang, Ting Xie, Ningshan Liu, Huaiyong Chen, Yan Geng, Adrianne Kurkciyan, Jessica Monterrosa Mena, Barry R Stripp, Dianhua Jiang, Paul W Noble
Successful recovery from lung injury requires the repair and regeneration of alveolar epithelial cells to restore the integrity of gas-exchanging regions within the lung and preserve organ function. Improper regeneration of the alveolar epithelium is often associated with severe pulmonary fibrosis, the latter of which involves the recruitment and activation of fibroblasts, as well as matrix accumulation. Type 2 alveolar epithelial cells (AEC2s) are stem cells in the adult lung that contribute to the lung repair process...
October 3, 2016: Nature Medicine
E G Skurikhin, A V Pakhomova, V A Krupin, O V Pershina, E S Pan, L A Ermolaeva, O E Vaizova, O Yu Rybalkina, A M Dygai
Inflammation, extracellular matrix proteins (hydroxyproline, connective tissue growth factor, collagen, and fibronectin), stem and progenitor cells (multipotent mesenchymal stromal cells, Clara cells, angiogenesis, precursors, endothelial and epithelial cells) were studied in female C57Bl/6 mice with experimental elastase-induced emphysema. Diffuse emphysema reduced the number of endothelial (CD45(-)CD31(+)CD34(+)) and epithelial (CD45(-)CD117(+)CD49f(+)) cells, induced microcirculation disturbances, and decreased the area occupied by the connective tissue...
August 2016: Bulletin of Experimental Biology and Medicine
Usua Laresgoiti, Marko Z Nikolić, Chandrika Rao, Jane L Brady, Rachel V Richardson, Emma J Batchen, Karen E Chapman, Emma L Rawlins
Insufficient alveolar gas exchange capacity is a major contributor to lung disease. During lung development, a population of distal epithelial progenitors first produce bronchiolar-fated and subsequently alveolar-fated progeny. The mechanisms controlling this bronchiolar to alveolar developmental transition remain largely unknown. We developed a novel grafting assay to test if lung epithelial progenitors are intrinsically programmed or if alveolar cell identity is determined by environmental factors. These experiments revealed that embryonic lung epithelial identity is extrinsically determined...
August 30, 2016: Development
Yang Liu, Bi-Jie Jiang, Run-Zhen Zhao, Hong-Long Ji
Regeneration of the epithelium of mammalian lungs is essential for restoring normal function following injury, and various cells and mechanisms contribute to this regeneration and repair. Club cells, bronchioalveolar stem cells (BASCs), and alveolar type II epithelial cells (ATII) are dominant stem/progenitor cells for maintaining epithelial turnover and repair. Epithelial Na(+) channels (ENaC), a critical pathway for transapical salt and fluid transport, are expressed in lung epithelial progenitors, including club and ATII cells...
2016: International Journal of Biological Sciences
Marie-Hélène Perruchot, Magdalena Arévalo-Turrubiarte, Florence Dufreneix, Laurence Finot, Vanessa Lollivier, Eric Chanat, Frédérique Mayeur, Frédéric Dessauge
The plasticity of the mammary gland relies on adult mammary stem cells (MaSCs) and their progenitors, which give rise to various populations of mammary epithelial cells (MECs). To face global challenges, an in-depth characterization of milk-producing animal mammary gland plasticity is required, to select more sustainable and robust dairy cows. The identification and characterization of MaSC and their progenitors will also provide innovative tools in veterinary/human medicine regarding mammary tissue damage (carcinogenesis, bacterial infections)...
October 1, 2016: Stem Cells and Development
N F Smirnova, A C Schamberger, S Nayakanti, R Hatz, J Behr, O Eickelberg
BACKGROUND: In the human lung, epithelial progenitor cells in the airways give rise to the differentiated pseudostratified airway epithelium. In mice, emerging evidence confers a progenitor function to cytokeratin 5 (KRT5(+)) or cytokeratin 14 (KRT14(+))-positive basal cells of the airway epithelium. Little is known, however, about the distribution of progenitor subpopulations in the human lung, particularly about aberrant epithelial differentiation in lung disease, such as idiopathic pulmonary fibrosis (IPF)...
2016: Respiratory Research
Maria Loscertales, Fotini Nicolaou, Marion Jeanne, Mauro Longoni, Douglas B Gould, Yunwei Sun, Faouzi I Maalouf, Nandor Nagy, Patricia K Donahoe
BACKGROUND: Type IV collagen is the main component of the basement membrane that gives strength to the blood-gas barrier (BGB). In mammals, the formation of a mature BGB occurs primarily after birth during alveologenesis and requires the formation of septa from the walls of the saccule. In contrast, in avians, the formation of the BGB occurs rapidly and prior to hatching. Mutation in basement membrane components results in an abnormal alveolar phenotype; however, the specific role of type IV collagen in regulating alveologenesis remains unknown...
2016: BMC Biology
Po-Nien Tsao, Chisa Matsuoka, Shu-Chen Wei, Atsuyasu Sato, Susumu Sato, Koichi Hasegawa, Hung-Kuan Chen, Thai-Yen Ling, Munemasa Mori, Wellington V Cardoso, Mitsuru Morimoto
Abnormal enlargement of the alveolar spaces is a hallmark of conditions such as chronic obstructive pulmonary disease and bronchopulmonary dysplasia. Notch signaling is crucial for differentiation and regeneration and repair of the airway epithelium. However, how Notch influences the alveolar compartment and integrates this process with airway development remains little understood. Here we report a prominent role of Notch signaling in the epithelial-mesenchymal interactions that lead to alveolar formation in the developing lung...
July 19, 2016: Proceedings of the National Academy of Sciences of the United States of America
Jennifer Quantius, Carole Schmoldt, Ana I Vazquez-Armendariz, Christin Becker, Elie El Agha, Jochen Wilhelm, Rory E Morty, István Vadász, Konstantin Mayer, Stefan Gattenloehner, Ludger Fink, Mikhail Matrosovich, Xiaokun Li, Werner Seeger, Juergen Lohmeyer, Saverio Bellusci, Susanne Herold
Influenza Virus (IV) pneumonia is associated with severe damage of the lung epithelium and respiratory failure. Apart from efficient host defense, structural repair of the injured epithelium is crucial for survival of severe pneumonia. The molecular mechanisms underlying stem/progenitor cell mediated regenerative responses are not well characterized. In particular, the impact of IV infection on lung stem cells and their regenerative responses remains elusive. Our study demonstrates that a highly pathogenic IV infects various cell populations in the murine lung, but displays a strong tropism to an epithelial cell subset with high proliferative capacity, defined by the signature EpCamhighCD24lowintegrin(α6)high...
June 2016: PLoS Pathogens
Shigemi Matsuyama, James Palmer, Adam Bates, Izmarie Poventud-Fuentes, Kelvin Wong, Justine Ngo, Mieko Matsuyama
Cells with DNA damage undergo apoptosis or cellular senescence if the damage cannot be repaired. Recent studies highlight that cellular senescence plays a major role in aging. However, age-associated diseases, including emphysema and neurodegenerative disorders, are caused by apoptosis of lung alveolar epithelial cells and neurons, respectively. Therefore, enhanced apoptosis also promotes aging and shortens the life span depending on the cell type. Recently, we reported that ku70(-) (/) (-)bax(-) (/) (-) and ku70(-) (/) (-)bax(+/) (-) mice showed significantly extended life span in comparison with ku70(-) (/) (-)bax(+/+) mice...
June 2016: Experimental Biology and Medicine
Mohammed I Ahmed, Salah Elias, Arne W Mould, Elizabeth K Bikoff, Elizabeth J Robertson
Mammary gland morphogenesis depends on a tight balance between cell proliferation, differentiation and apoptosis, to create a defined functional hierarchy within the epithelia. The limited availability of stem cell/progenitor markers has made it challenging to decipher lineage relationships. Here, we identify a rare subset of luminal progenitors that express the zinc finger transcriptional repressor Blimp1, and demonstrate that this subset of highly clonogenic luminal progenitors is required for mammary gland development...
May 15, 2016: Development
Chihiro Ozawa, Michiko Horiguchi, Tomomi Akita, Yuki Oiso, Kaori Abe, Tomoki Motomura, Chikamasa Yamashita
Pulmonary emphysema is a disease in which lung alveoli are irreversibly damaged, thus compromising lung function. Our previous study revealed that all-trans-retinoic acid (ATRA) induces the differentiation of human lung alveolar epithelial type 2 progenitor cells and repairs the alveoli of emphysema model mice. ATRA also reportedly has the ability to activate peroxisome proliferator-activated receptor (PPAR) β/δ. A selective PPARβ/δ ligand has been reported to induce the differentiation of human keratinocytes during wound repair...
2016: Biological & Pharmaceutical Bulletin
Xiaoru Wang, Yi Wang, Melinda E Snitow, Kathleen M Stewart, Shanru Li, MinMin Lu, Edward E Morrisey
The commitment and differentiation of the alveolar type I (AT1) cell lineage is a critical step for the formation of distal lung saccules, which are the primitive alveolar units required for postnatal respiration. How AT1 cells arise from the distal lung epithelial progenitor cells prior to birth and whether this process depends on a developmental niche instructed by mesenchymal cells is poorly understood. We show that mice lacking histone deacetylase 3 specifically in the developing lung mesenchyme display lung hypoplasia including decreased mesenchymal proliferation and a severe impairment of AT1 cell differentiation...
June 15, 2016: Developmental Biology
Cho-Ming Chao, Alena Moiseenko, Klaus-Peter Zimmer, Saverio Bellusci
BACKGROUND: Alveologenesis is the last stage in lung development and is essential for building the gas-exchanging units called alveoli. Despite intensive lung research, the intricate crosstalk between mesenchymal and epithelial cell lineages during alveologenesis is poorly understood. This crosstalk contributes to the formation of the secondary septae, which are key structures of healthy alveoli. CONCLUSIONS: A better understanding of the cellular and molecular processes underlying the formation of the secondary septae is critical for the development of new therapies to protect or regenerate the alveoli...
December 2016: Molecular and Cellular Pediatrics
T Kato, K Oka, T Nakamura, A Ito
Organ-specific stem cells play key roles in maintaining the epithelial cell layers of lung. Bronchioalveolar stem cells (BASCs) are distal lung epithelial stem cells of adult mice. Alveolar type 2 (AT2) cells have important functions and serve as progenitor cells of alveolar type 1 (AT1) cells to repair the epithelium when they are injured. Hepatocyte growth factor (HGF) elicits mitogenic, morphogenic, and anti-apoptotic effects on lung epithelial cells through tyrosine phosphorylation of Met receptor, and thus is recognized as a pulmotrophic factor...
2016: European Journal of Histochemistry: EJH
Min Yee, Robert Gelein, Thomas J Mariani, B Paige Lawrence, Michael A O'Reilly
Alveolar epithelial type II cells (AEC2) maintain pulmonary homeostasis by producing surfactant, expressing innate immune molecules, and functioning as adult progenitor cells for themselves and alveolar epithelial type I cells (AEC1). How the proper number of alveolar epithelial cells is determined in the adult lung is not well understood. Here, BrdU labeling, genetic lineage tracing, and targeted expression of the anti-oxidant extracellular superoxide dismutase in AEC2s are used to show how the oxygen environment at birth influences postnatal expansion of AEC2s and AEC1s in mice...
May 2016: Stem Cells
Vladimir Ustiyan, Yufang Zhang, Anne-Karina T Perl, Jeffrey A Whitsett, Tanya V Kalin, Vladimir V Kalinichenko
BACKGROUND: Lung morphogenesis is regulated by interactions between the canonical Wnt/β-catenin and Kras/ERK/Foxm1 signaling pathways that establish proximal-peripheral patterning of lung tubules. How these interactions influence the development of respiratory epithelial progenitors to acquire airway as compared to alveolar epithelial cell fate is unknown. During branching morphogenesis, SOX9 transcription factor is normally restricted from conducting airway epithelial cells and is highly expressed in peripheral, acinar progenitor cells that serve as precursors of alveolar type 2 (AT2) and AT1 cells as the lung matures...
May 2016: Developmental Dynamics: An Official Publication of the American Association of Anatomists
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