Human embryonic lung epithelial tips are multipotent progenitors that can be expanded in vitro as long-term self-renewing organoids

被引:0
作者
Nikolic, Marko Z. [1 ]
Caritg, Oriol [1 ]
Jeng, Quitz [1 ]
Johnson, Jo-Anne [1 ]
Sun, Dawei [1 ]
Howell, Kate J. [2 ,3 ]
Brady, Jane L. [1 ]
Laresgoiti, Usua [1 ]
Allen, George [1 ]
Butler, Richard [1 ]
Zilbauer, Matthias [2 ,4 ,5 ]
Giangreco, Adam [6 ]
Rawlins, Emma L. [1 ,7 ,8 ]
机构
[1] Univ Cambridge, Wellcome Trust CRUK Gurdon Inst, Cambridge, England
[2] Univ Cambridge, Dept Paediat, Cambridge, MA USA
[3] European Bioinformat Inst, European Mol Biol Lab, Wellcome Genome Campus, Cambridge, England
[4] Univ Cambridge, Dept Paediat Gastroenterol, Cambridge, England
[5] Addenbrookes Hosp, Cambridge, England
[6] UCL, UCL Resp, Lungs Living Res Ctr, London, England
[7] Univ Cambridge, Dept Pathol, Cambridge, England
[8] Wellcome Trust MRC Stem Cell Inst, Cambridge, England
来源
ELIFE | 2017年 / 6卷
基金
英国医学研究理事会;
关键词
HUMAN FETAL LUNG; LARGE GENE LISTS; STEM-CELLS; MOUSE LUNG; NEUROENDOCRINE DIFFERENTIATION; BRANCHING MORPHOGENESIS; RESPIRATORY EPITHELIUM; INTESTINAL ORGANOIDS; TRANSCRIPTION FACTOR; ALVEOLAR CELLS;
D O I
10.7554/eLife.26575.001
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
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. These experiments confirm that human and mouse tips are analogous and identify signalling pathways that are sufficient for long-term self-renewal of human tips as differentiation-competent organoids. Moreover, we identify mouse-human differences, including markers that define progenitor states and signalling requirements for long-term self-renewal. Our organoid system provides a genetically-tractable tool that will allow these human-specific features of lung development to be investigated.
引用
收藏
页数:33
相关论文
共 74 条
[1]   Evidence for the involvement of fibroblast growth factor 10 in lipofibroblast formation during embryonic lung development [J].
Al Alam, Denise ;
El Agha, Elie ;
Sakurai, Reiko ;
Kheirollahi, Vahid ;
Moiseenko, Alena ;
Danopoulos, Soula ;
Shrestha, Amit ;
Schmoldt, Carole ;
Quantius, Jennifer ;
Herold, Susanne ;
Chao, Cho-Ming ;
Tiozzo, Caterina ;
De Langhe, Stijn ;
Plikus, Maksim V. ;
Thornton, Matthew ;
Grubbs, Brendan ;
Minoo, Parviz ;
Rehan, Virender K. ;
Bellusci, Saverio .
DEVELOPMENT, 2015, 142 (23) :4139-4150
[2]   Two nested developmental waves demarcate a compartment boundary in the mouse lung [J].
Alanis, Denise Martinez ;
Chang, Daniel R. ;
Akiyama, Haruhiko ;
Krasnow, Mark A. ;
Chen, Jichao .
NATURE COMMUNICATIONS, 2014, 5
[3]   INDUCTION IN VITRO OF TRACHEAL BUDS BY PULMONARY MESENCHYME GRAFTED ON TRACHEAL EPITHELIUM [J].
ALESCIO, T ;
CASSINI, A .
JOURNAL OF EXPERIMENTAL ZOOLOGY, 1962, 150 (02) :83-&
[4]   Type 2 alveolar cells are stem cells in adult lung [J].
Barkauskas, Christina E. ;
Cronce, Michael J. ;
Rackley, Craig R. ;
Bowie, Emily J. ;
Keene, Douglas R. ;
Stripp, Barry R. ;
Randell, Scott H. ;
Noble, Paul W. ;
Hogan, Brigid L. M. .
JOURNAL OF CLINICAL INVESTIGATION, 2013, 123 (07) :3025-3036
[5]  
Bellusci S, 1996, DEVELOPMENT, V122, P1693
[6]  
Bellusci S, 1997, DEVELOPMENT, V124, P53
[7]   The miR-200 Family and Its Targets Regulate Type II Cell Differentiation in Human Fetal Lung [J].
Benlhabib, Houda ;
Guo, Wei ;
Pierce, Brianne M. ;
Mendelson, Carole R. .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2015, 290 (37) :22409-22422
[8]   The NIH Roadmap Epigenomics Mapping Consortium [J].
Bernstein, Bradley E. ;
Stamatoyannopoulos, John A. ;
Costello, Joseph F. ;
Ren, Bing ;
Milosavljevic, Aleksandar ;
Meissner, Alexander ;
Kellis, Manolis ;
Marra, Marco A. ;
Beaudet, Arthur L. ;
Ecker, Joseph R. ;
Farnham, Peggy J. ;
Hirst, Martin ;
Lander, Eric S. ;
Mikkelsen, Tarjei S. ;
Thomson, James A. .
NATURE BIOTECHNOLOGY, 2010, 28 (10) :1045-1048
[9]   Angiosarcomas express mixed endothelial phenotypes of blood and lymphatic capillaries -: Podoplanin as a specific marker for lymphatic endothelium [J].
Breiteneder-Geleff, S ;
Soleiman, A ;
Kowalski, H ;
Horvat, R ;
Amann, G ;
Kriehuber, E ;
Diem, K ;
Weninger, W ;
Tschachler, E ;
Alitalo, K ;
Kerjaschki, D .
AMERICAN JOURNAL OF PATHOLOGY, 1999, 154 (02) :385-394
[10]   FETAL AND POSTNATAL-DEVELOPMENT OF THE LUNG [J].
BURRI, PH .
ANNUAL REVIEW OF PHYSIOLOGY, 1984, 46 :617-628