scholarly journals Prospective isolation of NKX2-1–expressing human lung progenitors derived from pluripotent stem cells

2017 ◽  
Vol 127 (6) ◽  
pp. 2277-2294 ◽  
Author(s):  
Finn Hawkins ◽  
Philipp Kramer ◽  
Anjali Jacob ◽  
Ian Driver ◽  
Dylan C. Thomas ◽  
...  
2015 ◽  
Vol 117 (suppl_1) ◽  
Author(s):  
zaniar ghazizadeh ◽  
Faranak Fattahi ◽  
Mehdi Sharifi ◽  
Sara Tale Ahmad ◽  
Parisa Shabani ◽  
...  

The secondary heart field (SHF) progenitors ultimately contributes to diverse cardiovascular cell types through the formation of an early, multipotent heart progenitor pool and are marked by expression of ISL1, a LIM-homeodomain transcription factor. Human SHF can be derived from human pluripotent stem cells but their characterization has been limited due to the inefficiency of the differentiation protocols and lack of a proper reporter or surface marker based purification system. Using genetic tools and antibiotic selection we were able to purify ISL1+ cells for global gene expression analysis to identify key pathways that SHF identity. Genetic and small molecule based manipulation of these pathways alter ISL1 induction in differentiating cultures. Further proteomic analysis of enriched ISL1+ cells identified a hit surface marker that enables prospective isolation of ISL1+ secondary heart field progenitor cells with more than 90% purity. Purified SHF cells were multipotent and differentiate into pacemaker cells, endothelial and smooth muscle cells as well as mature beating cardiomyocytes. Finally transplantation of hPSC-derived purified SHF progenitors using this surface marker, restored myocardial function and regenerated infarcted area in mice myocardial infarction model.


2021 ◽  
Author(s):  
Chaido Ori ◽  
Meshal Ansari ◽  
Ilias Angelidis ◽  
Fabian J. Theis ◽  
Herbert B. Schiller ◽  
...  

ABSTRACTUnderstanding the development of human respiratory tissues is crucial for modeling and treating lung disorders. The molecular details for the specification of lung progenitors from human pluripotent stem cells (hPSCs) are unclear. Here, we use single cell RNA-sequencing with high temporal resolution along an optimized differentiation protocol to determine the transcriptional hierarchy of lung specification from human hPSCs and map out the underlying single cell trajectories. We show that Sonic hedgehog, TGF-β and Notch activation are required in an ISL1/NKX2-1 trajectory that gives rise to lung progenitors during the foregut endoderm stage. Induction of HHEX marks an alternative trajectory at the early definitive endoderm stage, which precedes the lung trajectory and generates a major hepatoblast population. Moreover, neither KDR+ nor mesendoderm progenitors are apparent intermediate states of lung and hepatic lineages. Our hierarchical multistep model predicts mechanisms leading to lung organogenesis, and creates a basis for studying early human lung development, as well as hPSC based disease and drug research.Abstract Figure


Author(s):  
Finn J. Hawkins ◽  
Tyler A. Longmire ◽  
Laertis Ikonomou ◽  
Jeremy Song ◽  
Harald Ott ◽  
...  

2017 ◽  
Vol 19 (5) ◽  
pp. 542-549 ◽  
Author(s):  
Ya-Wen Chen ◽  
Sarah Xuelian Huang ◽  
Ana Luisa Rodrigues Toste de Carvalho ◽  
Siu-Hong Ho ◽  
Mohammad Naimul Islam ◽  
...  

2012 ◽  
Vol 2 (1) ◽  
Author(s):  
Katsutsugu Umeda ◽  
Jiangang Zhao ◽  
Paul Simmons ◽  
Edouard Stanley ◽  
Andrew Elefanty ◽  
...  

2010 ◽  
Vol 34 (8) ◽  
pp. S36-S36
Author(s):  
Ping Duan ◽  
Xuelin Ren ◽  
Wenhai Yan ◽  
Xuefei Han ◽  
Xu Yan ◽  
...  

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