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Alveolar epithelial progenitor

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https://www.readbyqxmd.com/read/29106405/isolation-and-3d-expansion-of-multipotent-sox9-mouse-lung-progenitors
#1
Massimo Nichane, Asif Javed, V Sivakamasundari, Monisha Ganesan, Lay Teng Ang, Petra Kraus, Thomas Lufkin, Kyle M Loh, Bing Lim
Multiple adult tissues are maintained by stem cells of restricted developmental potential which can only form a subset of lineages within the tissue. For instance, the two adult lung epithelial compartments (airways and alveoli) are separately maintained by distinct lineage-restricted stem cells. A challenge has been to obtain multipotent stem cells and/or progenitors that can generate all epithelial cell types of a given tissue. Here we show that mouse Sox9(+) multipotent embryonic lung progenitors can be isolated and expanded long term in 3D culture...
November 6, 2017: Nature Methods
https://www.readbyqxmd.com/read/29070831/inhibition-of-lobuloalveolar-development-by-foxc1-overexpression-in-the-mouse-mammary-gland
#2
Bowen Gao, Ying Qu, Bingchen Han, Yoshiko Nagaoka, Makoto Katsumata, Nan Deng, Shikha Bose, Liting Jin, Armando E Giuliano, Xiaojiang Cui
The forkhead box transcription factor FOXC1 plays a critical role in embryogenesis and the development of many organs. Its mutations and high expression are associated with many human diseases including breast cancer. Although FOXC1 knockout mouse studies showed that it is not required for mammary gland development during puberty, it is not clear whether its overexpression alters normal mammary development in vivo. To address this question, we generated transgenic mice with mammary-specific FOXC1 overexpression...
October 25, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29056548/human-induced-pluripotent-stem-cell-derived-lung-progenitor-and-alveolar-epithelial-cells-attenuate-hyperoxia-induced-lung-injury
#3
Mehdi Shafa, Lavinia Iuliana Ionescu, Arul Vadivel, Jennifer J P Collins, Liqun Xu, Shumei Zhong, Martin Kang, Geneviève de Caen, Manijeh Daneshmand, Jenny Shi, Katherine Z Fu, Andrew Qi, Ying Wang, James Ellis, William L Stanford, Bernard Thébaud
BACKGROUND AIMS: Bronchopulmonary dysplasia (BPD), a chronic lung disease characterized by disrupted lung growth, is the most common complication in extreme premature infants. BPD leads to persistent pulmonary disease later in life. Alveolar epithelial type 2 cells (AEC2s), a subset of which represent distal lung progenitor cells (LPCs), promote normal lung growth and repair. AEC2 depletion may contribute to persistent lung injury in BPD. We hypothesized that induced pluripotent stem cell (iPSC)-derived AECs prevent lung damage in experimental oxygen-induced BPD...
October 20, 2017: Cytotherapy
https://www.readbyqxmd.com/read/29029397/tsp1-promotes-alveolar-stem-cell-proliferation-and-its-down-regulation-relates-to-lung-inflammation-in-intralobar-pulmonary-sequestration
#4
Kuan Li, Qi Wu, Xin Sun, Yan Geng, Dong Leng, Hongwei Li, Subei Zhang, Qiaoxing Wang, Junping Wu, Long Xu, Xue Li, Yu Li, Qiuyang Zhang, Adrianne Kurkciyan, Jiurong Liang, Dianhua Jiang, Huaiyong Chen
An aberrant systemic artery supply results in recurrent infections in the abnormal lung lobe of intralobar pulmonary sequestration (ILS). The mechanisms underlying such persistent inflammation are unknown. Here, we hypothesize that alteration of an endothelial cell niche for alveolar epithelial cells results in the impaired proliferation potential of alveolar progenitor cells, leading to the defective defense mechanism in intralobar pulmonary sequestration. Paraffin sections of lung tissues from patients with intralobar pulmonary sequestration or from healthy controls were collected for analysis of alveolar epithelial alterations in intralobar pulmonary sequestration by quantitative RT-PCR or immunofluorescent staining...
September 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/28967890/long-term-expansion-of-alveolar-stem-cells-derived-from-human-ips-cells-in-organoids
#5
Yuki Yamamoto, Shimpei Gotoh, Yohei Korogi, Masahide Seki, Satoshi Konishi, Satoshi Ikeo, Naoyuki Sone, Tadao Nagasaki, Hisako Matsumoto, Shigeo Muro, Isao Ito, Toyohiro Hirai, Takashi Kohno, Yutaka Suzuki, Michiaki Mishima
The stable expansion of tissue-specific stem cells in vitro has contributed to research on several organs. Alveolar epithelial type II (AT2) cells function as tissue stem cells in the lung, but robust models for studying human AT2 cells are lacking. Here we report a method for the efficient generation and long-term expansion of alveolar organoids (AOs) harboring SFTPC(+) alveolar stem cells derived from human induced pluripotent stem cells (hiPSCs). hiPSC-derived SFTPC(+) cells self-renewed, with transcriptomes and morphology consistent with those of AT2 cells, and were able to differentiate into alveolar epithelial type I (AT1)-like cells...
November 2017: Nature Methods
https://www.readbyqxmd.com/read/28965766/differentiation-of-human-pluripotent-stem-cells-into-functional-lung-alveolar-epithelial-cells
#6
Anjali Jacob, Michael Morley, Finn Hawkins, Katherine B McCauley, J C Jean, Hillary Heins, Cheng-Lun Na, Timothy E Weaver, Marall Vedaie, Killian Hurley, Anne Hinds, Scott J Russo, Seunghyi Kook, William Zacharias, Matthias Ochs, Katrina Traber, Lee J Quinton, Ana Crane, Brian R Davis, Frances V White, Jennifer Wambach, Jeffrey A Whitsett, F Sessions Cole, Edward E Morrisey, Susan H Guttentag, Michael F Beers, Darrell N Kotton
Lung alveoli, which are unique to air-breathing organisms, have been challenging to generate from pluripotent stem cells (PSCs) in part because there are limited model systems available to provide the necessary developmental roadmaps for in vitro differentiation. Here we report the generation of alveolar epithelial type 2 cells (AEC2s), the facultative progenitors of lung alveoli, from human PSCs. Using multicolored fluorescent reporter lines, we track and purify human SFTPC+ alveolar progenitors as they emerge from endodermal precursors in response to stimulation of Wnt and FGF signaling...
October 5, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/28936122/depletion-of-club-cells-attenuates-bleomycin-induced-lung-injury-and-fibrosis-in-mice
#7
Tetsuya Yokoyama, Toyoshi Yanagihara, Kunihiro Suzuki, Naoki Hamada, Kazuya Tsubouchi, Saiko Ogata-Suetsugu, Hironori Mikumo, Chika Ikeda-Harada, Takashige Maeyama, Kazuyoshi Kuwano, Yoichi Nakanishi
BACKGROUND: The role of bronchiolar epithelial cells in the pathogenesis of pulmonary fibrosis has not been clarified. We previously demonstrated DNA damage in murine bronchioles in the early stages of bleomycin-induced pulmonary fibrosis that subsequently extended to alveolar cells at the advanced stages of the disease. Club cells are progenitor cells for bronchioles and are known to play protective roles against lung inflammation and damage. The aim of the present study was to elucidate the role of club cells in the development of pulmonary fibrosis...
2017: Journal of Inflammation
https://www.readbyqxmd.com/read/28916766/stimulatory-secretions-of-airway-epithelial-cells-accelerate-early-repair-of-tracheal-epithelium
#8
Egi Kardia, Rafeezul Mohamed, Badrul Hisham Yahaya
Airway stem/progenitor epithelial cells (AECs) are notable for their differentiation capacities in response to lung injury. Our previous finding highlighted the regenerative capacity of AECs following transplantation in repairing tracheal injury and reducing the severity of alveolar damage associated acute lung injury in a rabbit model. The goal of this study is to further investigate the potential of AECs to re-populate the tracheal epithelium and to study their stimulatory effect on inhibiting pro-inflammatory cytokines, epithelial cell migration and proliferation, and epithelial-to-mesenchymal transition (EMT) process following tracheal injury...
September 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28886383/anatomically-and-functionally-distinct-lung-mesenchymal-populations-marked-by-lgr5-and-lgr6
#9
Joo-Hyeon Lee, Tuomas Tammela, Matan Hofree, Jinwook Choi, Nemanja Despot Marjanovic, Seungmin Han, David Canner, Katherine Wu, Margherita Paschini, Dong Ha Bhang, Tyler Jacks, Aviv Regev, Carla F Kim
The diversity of mesenchymal cell types in the lung that influence epithelial homeostasis and regeneration is poorly defined. We used genetic lineage tracing, single-cell RNA sequencing, and organoid culture approaches to show that Lgr5 and Lgr6, well-known markers of stem cells in epithelial tissues, are markers of mesenchymal cells in the adult lung. Lgr6(+) cells comprise a subpopulation of smooth muscle cells surrounding airway epithelia and promote airway differentiation of epithelial progenitors via Wnt-Fgf10 cooperation...
September 7, 2017: Cell
https://www.readbyqxmd.com/read/28886382/distinct-mesenchymal-lineages-and-niches-promote-epithelial-self-renewal-and-myofibrogenesis-in-the-lung
#10
Jarod A Zepp, William J Zacharias, David B Frank, Christina A Cavanaugh, Su Zhou, Michael P Morley, Edward E Morrisey
The lung is an architecturally complex organ comprising a heterogeneous mixture of various epithelial and mesenchymal lineages. We use single-cell RNA sequencing and signaling lineage reporters to generate a spatial and transcriptional map of the lung mesenchyme. We find that each mesenchymal lineage has a distinct spatial address and transcriptional profile leading to unique niche regulatory functions. The mesenchymal alveolar niche cell is Wnt responsive, expresses Pdgfrα, and is critical for alveolar epithelial cell growth and self-renewal...
September 7, 2017: Cell
https://www.readbyqxmd.com/read/28780147/stem-cells-in-pulmonary-disease-and-regeneration
#11
REVIEW
Rohan R Nadkarni, Soumeya Abed, Jonathan S Draper
The epithelial cells lining the mammalian lung are subjected to constant interaction with the external environment, necessitating robust regeneration strategies to deal with cell loss due to natural turnover or damage arising from inhaled agents or disease. Since lung epithelial function extends beyond respiratory gas exchange to include roles such as immune defense and mucociliary clearance, a diverse complement of epithelial cell types exists that are regionally distributed along the respiratory tree and extensive surface area of the alveolar interface...
August 2, 2017: Chest
https://www.readbyqxmd.com/read/28737769/local-lung-hypoxia-determines-epithelial-fate-decisions-during-alveolar-regeneration
#12
Ying Xi, Thomas Kim, Alexis N Brumwell, Ian H Driver, Ying Wei, Victor Tan, Julia R Jackson, Jianming Xu, Dong-Kee Lee, Jeffrey E Gotts, Michael A Matthay, John M Shannon, Harold A Chapman, Andrew E Vaughan
After influenza infection, lineage-negative epithelial progenitors (LNEPs) exhibit a binary response to reconstitute epithelial barriers: activating a Notch-dependent ΔNp63/cytokeratin 5 (Krt5) remodelling program or differentiating into alveolar type II cells (AEC2s). Here we show that local lung hypoxia, through hypoxia-inducible factor (HIF1α), drives Notch signalling and Krt5(pos) basal-like cell expansion. Single-cell transcriptional profiling of human AEC2s from fibrotic lungs revealed a hypoxic subpopulation with activated Notch, suppressed surfactant protein C (SPC), and transdifferentiation toward a Krt5(pos) basal-like state...
August 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28675425/foxc2-influences-alveolar-epithelial-cell-differentiation-during-lung-development
#13
Mayoko Tsuji, Masae Morishima, Kazuhiko Shimizu, Shunichi Morikawa, Mikael Heglind, Sven Enerbäck, Taichi Ezaki, Jun Tamaoki
FOXC2, a forkhead transcriptional factor, is a candidate gene for congenital heart diseases and lymphedema-distichiasis syndrome and yellow nail syndrome; however, there are no reports on Foxc2 and the development of the lung. We have identified lung abnormalities in Foxc2-knockout embryos during investigation of cardiac development. The aim of this study was to clarify the morphological characteristics during lung development using ICR-Foxc2 knockout lungs. Mutant fetuses at embryonic days 10.5-18.5 were obtained from mating of Foxc2(+/-) mice and then analyzed...
July 4, 2017: Development, Growth & Differentiation
https://www.readbyqxmd.com/read/28595637/exosome-mir-371b-5p-promotes-proliferation-of-lung-alveolar-progenitor-type-ii-cells-by-using-pten-to-orchestrate-the-pi3k-akt-signaling
#14
Yuan Quan, Zhaohua Wang, Ling Gong, Xinmiao Peng, Melissa A Richard, Junlan Zhang, Myriam Fornage, Joseph L Alcorn, Dachun Wang
BACKGROUND: Pathways directing endogenous stem/progenitor cells to restore normal architecture and function of damaged/diseased lungs remain underexplored. Published data have revealed that alveolar progenitor type II cell (ATIIC)-derived signaling promotes re-epithelialization of injured alveoli, yet the underlying mechanism is unknown. Here we aim to define the role of ATIIC-derived exosome miRNA signaling in controlling ATIIC-specific proliferation or differentiation in response to injury...
June 8, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28538234/overview-of-lung-development-in-the-newborn-human
#15
David Warburton
In human neonates rapid adaptation from an aqueous intrauterine environment to permanent air breathing is the rate-limiting step for extrauterine life, failure of which justifies the existence of neonatal intensive care units. The lung develops at about 4-6 weeks' gestation in humans as a ventral outpouching of the primitive foregut into the surrounding ventral mesenchyme, termed the laryngotracheal groove. At its posterior end lie progenitor cells that form a pair of bronchial tubes, from which arise all the distal epithelial structures of the lung...
2017: Neonatology
https://www.readbyqxmd.com/read/28500076/stat5-is-required-for-cd103-dendritic-cell-and-alveolar-macrophage-development-and-protection-from-lung-injury
#16
William E Eddy, Ke-Qin Gong, Bryan Bell, William C Parks, Steven F Ziegler, Anne M Manicone
We tested the role of Stat5 in dendritic cell and alveolar macrophage (AM) homeostasis in the lung using CD11c-cre mediated deletion (Cre(+)5(f/f)). We show that Stat5 is required for CD103(+) dendritic cell and AM development. We found that fetal monocyte maturation into AMs was impaired in Cre(+)5(f/f) mice, and we also confirmed impaired AM development of progenitor cells using mixed chimera experiments. In the absence of Stat5 signaling in AMs, mice developed alveolar proteinosis with altered lipid homeostasis...
June 15, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28495456/crosstalk-between-stat5-activation-and-pi3k-akt-functions-in-normal-and-transformed-mammary-epithelial-cells
#17
REVIEW
Patrick D Rädler, Barbara L Wehde, Kay-Uwe Wagner
Janus kinases (JAKs) and signal transducers and activators of transcription (STATs) have been shown to function downstream of several peptide hormones and cytokines that are required for postnatal development and secretory function of the mammary gland. As part of an extended network, these signal transducers can engage in crosstalk with other pathways to facilitate synergistic, and sometimes antagonistic, actions of different growth factors. Specifically, signaling through the JAK2/STAT5 cascade has been demonstrated to be indispensable for the specification, proliferation, differentiation, and survival of secretory mammary epithelial cells...
August 15, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28451462/pulmonary-adenocarcinoma-with-mucin-production-modulates-phenotype-according-to-common-genetic-traits-a-reappraisal-of-mucinous-adenocarcinoma-and-colloid-adenocarcinoma
#18
Angelica Sonzogni, Fabrizio Bianchi, Alessandra Fabbri, Mara Cossa, Giulio Rossi, Alberto Cavazza, Elena Tamborini, Federica Perrone, Adele Busico, Iolanda Capone, Benedetta Picciani, Barbara Valeri, Ugo Pastorino, Giuseppe Pelosi
Whether invasive mucinous adenocarcinoma (IMA) and colloid adenocarcinoma (ICA) of the lung represent separate tumour entities, or simply lie within a spectrum of phenotypic variability, is worth investigating. Fifteen ICA, 12 IMA, 9 ALK-rearranged adenocarcinomas (ALKA), 8 non-mucinous KRAS-mutated adenocarcinomas (KRASA) and 9 mucinous breast adenocarcinomas (MBA) were assessed by immunohistochemistry for alveolar (TTF1, cytoplasmic MUC1), intestinal (CDX-2, MUC2), gastric (membrane MUC1, MUC6), bronchial (MUC5AC), mesenchymal (vimentin), neuroendocrine (chromogranin A, synaptophysin), sex steroid hormone-related (oestrogen and progesterone receptors), pan-mucinous (HNF4A) and pan-epithelial (keratin 7) lineage biomarkers and by targeted next generation sequencing (TNGS) for 50 recurrently altered cancer genes...
April 2017: Journal of Pathology. Clinical Research
https://www.readbyqxmd.com/read/28408205/temporal-spatial-and-phenotypical-changes-of-pdgfr%C3%AE-expressing-fibroblasts-during-late-lung-development
#19
Mehari Endale, Shawn Ahlfeld, Erik Bao, Xiaoting Chen, Jenna Green, Zach Bess, Matthew T Weirauch, Yan Xu, Anne Karina Perl
Many studies have investigated the source and role of epithelial progenitors during lung development; such information is limited for fibroblast populations and their complex role in the developing lung. In this study, we characterized the spatial location, mRNA expression and Immunophenotyping of PDGFRα(+) fibroblasts during sacculation and alveolarization. Confocal microscopy identified spatial association of PDGFRα expressing fibroblasts with proximal epithelial cells of the branching bronchioles and the dilating acinar tubules at E16...
May 15, 2017: Developmental Biology
https://www.readbyqxmd.com/read/28402849/uroplakin-3a-cells-are-a-distinctive-population-of-epithelial-progenitors-that-contribute-to-airway-maintenance-and-post-injury-repair
#20
Arjun Guha, Aditya Deshpande, Aradhya Jain, Paola Sebastiani, Wellington V Cardoso
There is evidence that certain club cells (CCs) in the murine airways associated with neuroepithelial bodies (NEBs) and terminal bronchioles are resistant to the xenobiotic naphthalene (Nap) and repopulate the airways after Nap injury. The identity and significance of these progenitors (variant CCs, v-CCs) have remained elusive. A recent screen for CC markers identified rare Uroplakin3a (Upk3a)-expressing cells (U-CCs) with a v-CC-like distribution. Here, we employ lineage analysis in the uninjured and chemically injured lungs to investigate the role of U-CCs as epithelial progenitors...
April 11, 2017: Cell Reports
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