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https://www.readbyqxmd.com/read/28737769/local-lung-hypoxia-determines-epithelial-fate-decisions-during-alveolar-regeneration
#1
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...
July 24, 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28723550/induced-pluripotent-stem-cell-derived-primitive-macrophages-provide-a-platform-for-modeling-tissue-resident-macrophage-differentiation-and-function
#2
Kazuyuki Takata, Tatsuya Kozaki, Christopher Zhe Wei Lee, Morgane Sonia Thion, Masayuki Otsuka, Shawn Lim, Kagistia Hana Utami, Kerem Fidan, Dong Shin Park, Benoit Malleret, Svetoslav Chakarov, Peter See, Donovan Low, Gillian Low, Marta Garcia-Miralles, Ruizhu Zeng, Jinqiu Zhang, Chi Ching Goh, Ahmet Gul, Sandra Hubert, Bernett Lee, Jinmiao Chen, Ivy Low, Nurhidaya Binte Shadan, Josephine Lum, Tay Seok Wei, Esther Mok, Shohei Kawanishi, Yoshihisa Kitamura, Anis Larbi, Michael Poidinger, Laurent Renia, Lai Guan Ng, Yochai Wolf, Steffen Jung, Tamer Önder, Evan Newell, Tara Huber, Eishi Ashihara, Sonia Garel, Mahmoud A Pouladi, Florent Ginhoux
Tissue macrophages arise during embryogenesis from yolk-sac (YS) progenitors that give rise to primitive YS macrophages. Until recently, it has been impossible to isolate or derive sufficient numbers of YS-derived macrophages for further study, but data now suggest that induced pluripotent stem cells (iPSCs) can be driven to undergo a process reminiscent of YS-hematopoiesis in vitro. We asked whether iPSC-derived primitive macrophages (iMacs) can terminally differentiate into specialized macrophages with the help of growth factors and organ-specific cues...
July 18, 2017: Immunity
https://www.readbyqxmd.com/read/28722352/serpine-1-induces-alveolar-type-ii-cell-senescence-through-activating-p53-p21-rb-pathway-in-fibrotic-lung-disease
#3
Chunsun Jiang, Gang Liu, Tracy Luckhardt, Veena Antony, Yong Zhou, A Brent Carter, Victor J Thannickal, Rui-Ming Liu
Senescence of alveolar type 2 (ATII) cells, progenitors of the alveolar epithelium, is implicated in the pathogeneses of idiopathic pulmonary fibrosis (IPF), an aging-related progressive fatal lung disorder with unknown etiology. The mechanism underlying ATII cell senescence in fibrotic lung diseases, however, remains poorly understood. In this study, we report that ATII cells in IPF lungs express higher levels of serpine 1, also known as plasminogen activator inhibitor 1 (PAI-1), and cell senescence markers p21 and p16, compared to ATII cells in control lungs...
July 19, 2017: Aging Cell
https://www.readbyqxmd.com/read/28705898/cellular-heterogeneity-in-the-ureteric-progenitor-niche-and-distinct-profiles-of-branching-morphogenesis-in-organ-development
#4
Elisabeth A Rutledge, Jean-Denis Benazet, Andrew P McMahon
Branching morphogenesis creates arborized epithelial networks. In the mammalian kidney, an epithelial progenitor pool at ureteric branch tips (UBT) creates the urine-transporting collecting system. Using region-specific mouse reporter strains, we performed an RNA-seq screen, identifying tip and stalk enriched gene sets in the developing collecting duct system. Detailed in situ hybridization studies of tip-enriched predictions identified UBT-enriched gene sets conserved between the mouse and human kidney. Comparative spatial analysis of their UBT niche expression highlighted distinct patterns of gene expression revealing novel molecular heterogeneity within the UBT progenitor population...
July 13, 2017: Development
https://www.readbyqxmd.com/read/28704777/preinvasive-disease-of-the-airway
#5
REVIEW
Ricky M Thakrar, Adam Pennycuick, Elaine Borg, Sam M Janes
Squamous cell carcinoma of the lung arises from preinvasive progenitors in the central airways. The archetypal model appears to be a stepwise morphological progression until there is invasion of the basement membrane. However, not every lesion appears to follow this course and many individuals can have stable disease, or indeed regress to normal epithelium. From our increased understanding of the molecular pathology it is becoming apparent that the respiratory epithelium accumulates progressive genetic and epigenetic insults in response to carcinogens...
July 2017: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/28702321/a-high-content-small-molecule-screen-identifies-novel-inducers-of-definitive-endoderm
#6
Alexander Korostylev, Pallavi U Mahaddalkar, Oliver Keminer, Kamyar Hadian, Kenji Schorpp, Philip Gribbon, Heiko Lickert
OBJECTIVES: Human embryonic stem cells (hESCs) and human induced pluripotent stem cells (hiPSCs) can generate any given cell type in the human body. One challenge for cell-replacement therapy is the efficient differentiation and expansion of large quantities of progenitor cells from pluripotent stem cells produced under good manufacturing practice (GMP). FOXA2 and SOX17 double positive definitive endoderm (DE) progenitor cells can give rise to all endoderm-derived cell types in the thymus, thyroid, lung, pancreas, liver, and gastrointestinal tract...
July 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/28695825/tsc2-disruption-in-mesenchymal-progenitors-results-in-tumors-with-vascular-anomalies-overexpressing-lgals3
#7
Peter J Klover, Rajesh L Thangapazham, Jiro Kato, Ji-An Wang, Stasia A Anderson, Victoria Hoffmann, Wendy K Steagall, Shaowei Li, Elizabeth McCart, Neera Nathan, Joshua D Bernstock, Matthew D Wilkerson, Clifton L Dalgard, Joel Moss, Thomas N Darling
Increased mTORC1 signaling from TSC1/TSC2 inactivation is found in cancer and causes tuberous sclerosis complex (TSC). The role of mesenchymal-derived cells in TSC tumorigenesis was investigated through disruption of Tsc2 in craniofacial and limb bud mesenchymal progenitors. Tsc2cKO(Prrx1-cre) mice had shortened lifespans and extensive hamartomas containing abnormal tortuous, dilated vessels prominent in the forelimbs. Abnormalities were blocked by the mTORC1 inhibitor sirolimus. A Tsc2/mTORC1 expression signature identified in Tsc2-deficient fibroblasts was also increased in bladder cancers with TSC1/TSC2 mutations in the TCGA database...
July 11, 2017: ELife
https://www.readbyqxmd.com/read/28681425/localization-of-relm-%C3%AE-fizz2-is-associated-with-cementum-formation
#8
Akihiro Hosoya, Akira Takahama, Hiroaki Nakamura
Resistin-like molecule-β/found in inflammatory zone 2 (RELM-β/FIZZ2) is a cysteine-rich secretory protein that is localized in the epithelium of the gastrointestinal tract and lung alveoli. Previous reports have suggested that this protein regulates glucose metabolism and inflammation. In the present study, to analyze the involvement of RELM-β/FIZZ2 in tooth development, we immunohistochemically examined the localization of RELM-β/FIZZ2 in tooth germs of embryonic days (E) 15-20 and postnatal days (P) 7-42 rats...
July 6, 2017: Anatomical Record: Advances in Integrative Anatomy and Evolutionary Biology
https://www.readbyqxmd.com/read/28676074/immunoregulatory-effects-of-multipotent-adult-progenitor-cells-in-a-porcine-ex-vivo-lung-perfusion-model
#9
An Martens, Sofie Ordies, Bart M Vanaudenaerde, Stijn E Verleden, Robin Vos, Dirk E Van Raemdonck, Geert M Verleden, Valerie D Roobrouck, Sandra Claes, Dominique Schols, Eric Verbeken, Catherine M Verfaillie, Arne P Neyrinck
BACKGROUND: Primary graft dysfunction (PGD) is considered to be the end result of an inflammatory response targeting the new lung allograft after transplant. Previous research has indicated that MAPC cell therapy might attenuate this injury by its paracrine effects on the pro-/anti-inflammatory balance. This study aims to investigate the immunoregulatory capacities of MAPC cells in PGD when administered in the airways. METHODS: Lungs of domestic pigs (n = 6/group) were subjected to 90 minutes of warm ischemia...
July 5, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28675425/foxc2-influences-alveolar-epithelial-cell-differentiation-during-lung-development
#10
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/28669077/lung-as-a-niche-for-hematopoietic-progenitors
#11
Isabella Borges, Isadora Sena, Patrick Azevedo, Julia Andreotti, Viviani Almeida, Ana Paiva, Gabryella Santos, Daniel Guerra, Pedro Prazeres, Luiza Lousado Mesquita, Luanny Souto de Barros Silva, Caroline Leonel, Akiva Mintz, Alexander Birbrair
Platelets are released from megakaryocytes. The bone marrow has been proposed to be the major site where this process occurs. Lefrançais et al. (2017) using state-of-the-art techniques including two-photon microscopy, in vivo lineage-tracing technologies, and sophisticated lung transplants reveal that the lung is also a primary site for platelet biogenesis. Strikingly, lung megakaryocytes can completely reconstitute platelet counts in the blood in mice with thrombocytopenia. This study also shows that hematopoietic progenitors, with capacity to repopulate the bone marrow after irradiation, are present in the lungs...
July 1, 2017: Stem Cell Reviews
https://www.readbyqxmd.com/read/28666430/derivation-of-therapeutic-lung-spheroid-cells-from-minimally-invasive-transbronchial-pulmonary-biopsies
#12
Phuong-Uyen C Dinh, Jhon Cores, M Taylor Hensley, Adam C Vandergriff, Junnan Tang, Tyler A Allen, Thomas G Caranasos, Kenneth B Adler, Leonard J Lobo, Ke Cheng
BACKGROUND: Resident stem and progenitor cells have been identified in the lung over the last decade, but isolation and culture of these cells remains a challenge. Thus, although these lung stem and progenitor cells provide an ideal source for stem-cell based therapy, mesenchymal stem cells (MSCs) remain the most popular cell therapy product for the treatment of lung diseases. Surgical lung biopsies can be the tissue source but such procedures carry a high risk of mortality. METHODS: In this study we demonstrate that therapeutic lung cells, termed "lung spheroid cells" (LSCs) can be generated from minimally invasive transbronchial lung biopsies using a three-dimensional culture technique...
June 30, 2017: Respiratory Research
https://www.readbyqxmd.com/read/28665271/human-embryonic-lung-epithelial-tips-are-multipotent-progenitors-that-can-be-expanded-in-vitro-as-long-term-self-renewing-organoids
#13
Marko Z Nikolić, Oriol Caritg, Quitz Jeng, Jo-Anne Johnson, Dawei Sun, Kate J Howell, Jane L Brady, Usua Laresgoiti, George Allen, Richard Butler, Matthias Zilbauer, Adam Giangreco, Emma L Rawlins
The embryonic mouse lung is a widely used substitute for human lung development. For example, attempts to differentiate human pluripotent stem cells to lung epithelium rely on passing through progenitor states that have only been described in mouse. The tip epithelium of the branching mouse lung is a multipotent progenitor pool that self-renews and produces differentiating descendants. We hypothesized that the human distal tip epithelium is an analogous progenitor population and tested this by examining morphology, gene expression and in vitro self-renewal and differentiation capacity of human tips...
June 30, 2017: ELife
https://www.readbyqxmd.com/read/28659499/intersections-of-lung-progenitor-cells-lung-disease-and-lung-cancer
#14
Carla F Kim
The use of stem cell biology approaches to study adult lung progenitor cells and lung cancer has brought a variety of new techniques to the field of lung biology and has elucidated new pathways that may be therapeutic targets in lung cancer. Recent results have begun to identify the ways in which different cell populations interact to regulate progenitor activity, and this has implications for the interventions that are possible in cancer and in a variety of lung diseases. Today's better understanding of the mechanisms that regulate lung progenitor cell self-renewal and differentiation, including understanding how multiple epigenetic factors affect lung injury repair, holds the promise for future better treatments for lung cancer and for optimising the response to therapy in lung cancer...
June 30, 2017: European Respiratory Review: An Official Journal of the European Respiratory Society
https://www.readbyqxmd.com/read/28659498/shared-epithelial-pathways-to-lung-repair-and-disease
#15
Magda Spella, Ioannis Lilis, Georgios T Stathopoulos
Chronic lung diseases present tremendous health burdens and share a common pathobiology of dysfunctional epithelial repair. Lung adenocarcinoma, the leading cancer killer worldwide, is caused mainly by chemical carcinogens of tobacco smoke that induce mutations in pulmonary epithelial cells leading to uncontrolled epithelial proliferation. Lung epithelial cells that possess the capacity for self-renewal and regeneration of other lung cell types are believed to underlie the pathobiology of chronic obstructive, fibrotic and neoplastic lung disorders...
June 30, 2017: European Respiratory Review: An Official Journal of the European Respiratory Society
https://www.readbyqxmd.com/read/28645296/myd88-dependent-pro-interleukin-1%C3%AE-induction-in-dendritic-cells-exposed-to-food-grade-synthetic-amorphous-silica
#16
Hans Christian Winkler, Julian Kornprobst, Peter Wick, Lea Maria von Moos, Ioannis Trantakis, Elisabeth Maria Schraner, Barbara Bathke, Hubertus Hochrein, Mark Suter, Hanspeter Naegeli
BACKGROUND: Dendritic cells (DCs) are specialized first-line sensors of foreign materials invading the organism. These sentinel cells rely on pattern recognition receptors such as Nod-like or Toll-like receptors (TLRs) to launch immune reactions against pathogens, but also to mediate tolerance to self-antigens and, in the intestinal milieu, to nutrients and commensals. Since inappropriate DC activation contributes to inflammatory diseases and immunopathologies, a key question in the evaluation of orally ingested nanomaterials is whether their contact with DCs in the intestinal mucosa disrupts this delicate homeostatic balance between pathogen defense and tolerance...
June 23, 2017: Particle and Fibre Toxicology
https://www.readbyqxmd.com/read/28634941/lungosphere-assay-3d-culture-of-lung-epithelial-stem-progenitor-cells
#17
Anas Rabata, Ales Hampl, Zuzana Koledova
Lung epithelium contains distinctive subpopulations of lung stem/progenitor cells (LSPCs) that are essential for lung epithelial maintenance and repair in vivo. Hence, LSPCs are in the center of interest of lung biology due to their promising therapeutic applications. To reach this goal, proper characterization of LSPCs, understanding of their proliferation and differentiation potentials and elucidation of mechanisms that control them are necessary. Therefore, development of reliable in vitro clonogenic assays has been needed...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28624051/persistent-injury-associated-anemia-the-role-of-the-bone-marrow-microenvironment
#18
Jessica K Millar, Kolenkode B Kannan, Tyler J Loftus, Ines G Alamo, Jessica Plazas, Philip A Efron, Alicia M Mohr
BACKGROUND: The regulation of erythropoiesis involves hematopoietic progenitor cells, bone marrow stroma, and the microenvironment. Following severe injury, a hypercatecholamine state develops that is associated with increased mobilization of hematopoietic progenitor cells to peripheral blood and decreased growth of bone marrow erythroid progenitor cells that manifests clinically as a persistent injury-associated anemia. Changes within the bone marrow microenvironment influence the development of erythroid progenitor cells...
June 15, 2017: Journal of Surgical Research
https://www.readbyqxmd.com/read/28620747/amniotic-fluid-cells-current-progress-and-emerging-challenges-in-renal-regeneration
#19
REVIEW
Stefano Da Sacco, Laura Perin, Sargis Sedrakyan
Amniotic fluid (AF) contains a heterogeneous population of cells that have been identified to possess pluripotent and progenitor-like characteristics. These cells have been applied in various regenerative medicine applications ranging from in vitro cell differentiation to tissue engineering to cellular therapies for different organs including the heart, the liver, the lung, and the kidneys. In this review, we examine the different methodologies used for the derivation of amniotic fluid stem cells and renal progenitors, and their application in renal repair and regeneration...
June 15, 2017: Pediatric Nephrology: Journal of the International Pediatric Nephrology Association
https://www.readbyqxmd.com/read/28619823/sin3a-regulates-epithelial-progenitor-cell-fate-during-lung-development
#20
Changfu Yao, Gianni Carraro, Bindu Konda, Xiangrong Guan, Takako Mizuno, Norika Chiba, Matthew Kostelny, Adrianne Kurkciyan, Gregory David, Jonathan L McQualter, Barry R Stripp
Mechanisms that regulate tissue-specific progenitors for maintenance and differentiation during development are poorly understood. Here, we demonstrate that the co-repressor protein Sin3a is critical for lung endoderm development. Loss of Sin3a in early foregut endoderm leads to a specific and profound defect in lung development with lung buds failing to undergo branching morphogenesis and progressive atrophy of the proximal lung endoderm with complete epithelial loss at later stages of development. Consequently, neonatal pups died at birth due to respiratory insufficiency...
June 15, 2017: Development
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