scholarly journals Human chondrogenic paraxial mesoderm, directed specification and prospective isolation from pluripotent stem cells

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


2017 ◽  
Vol 127 (6) ◽  
pp. 2277-2294 ◽  
Author(s):  
Finn Hawkins ◽  
Philipp Kramer ◽  
Anjali Jacob ◽  
Ian Driver ◽  
Dylan C. Thomas ◽  
...  

F1000Research ◽  
2015 ◽  
Vol 4 ◽  
pp. 100 ◽  
Author(s):  
Anestis Tsakiridis ◽  
Valerie Wilson

Retrospective clonal analysis in the mouse has demonstrated that the posterior spinal cord neurectoderm and paraxial mesoderm share a common bipotent progenitor. These neuromesodermal progenitors (NMPs) are the source of new axial structures during embryonic rostrocaudal axis elongation and are marked by the simultaneous co-expression of the transcription factors T(Brachyury) (T(Bra)) and Sox2. NMP-like cells have recently been derived from pluripotent stem cells in vitro following combined stimulation of Wnt and fibroblast growth factor (FGF) signaling. Under these conditions the majority of cultures consist of T(Bra)/Sox2 co-expressing cells after 48-72 hours of differentiation. Although the capacity of these cells to generate posterior neural and paraxial mesoderm derivatives has been demonstrated at the population level, it is unknown whether a single in vitro-derived NMP can give rise to both neural and mesodermal cells. Here we demonstrate that T(Bra) positive cells obtained from mouse epiblast stem cells (EpiSCs) after culture in NMP-inducing conditions can generate both neural and mesodermal clones. This finding suggests that, similar to their embryonic counterparts, in vitro-derived NMPs are truly bipotent and can thus be exploited as a model for studying the molecular basis of developmental cell fate decisions.


2015 ◽  
Vol 35 (suppl_1) ◽  
Author(s):  
Jiao Jiao ◽  
Wei Xiong ◽  
Lunchang Wang ◽  
Eugene Chen ◽  
Bo Yang

Ascending aortic aneurysm occurs in 35%-68% patients with bicuspid aortic valves (BAV), which is more frequently than it does in patients with normal trileaflet aortic valves (TAV). In contrast to recurrent aneurysms of the ascending aorta, descending aortic aneurysms is very rare in patients with BAV. Vascular Smooth Muscle Cells (SMCs) make up the media of the aortic walls, and their contractile properties help sustain vessel tone. Interestingly, ascending aorta is populated by SMCs arising from neural crest and descending aorta by SMCs from paraxial mesoderm. An intriguing hypothesis is that the distinct susceptibility of aneurysm in the ascending and descending aorta in patients with BAV is due in part to disparities in SMC embryonic origins. To prove our hypothesis, we used an induced Pluripotent Stem Cells (iPS) model system to generate SMCs from neural crest and paraxial mesoderm. Firstly, iPSCs were established from a patient with BAV and ascending thoracic aortic aneurysm (BAV/TAA) and two control patients with normal aorta and TAV. The iPSCs pluripotency was verified by standard stem cell markers and teratoma formation. Neural crest stem cells (NCSCs) were differentiated from iPSCs and expressed neural crest markers, including P75, HNK1, AP2 and Sox9. In parallel, paraxial mesoderm cells (PMCs) were differentiated from iPSCs and expressed specific markers, including TCF15, TBX6, Meox1 and Pax1. The SMCs differentiated from both lineages had expression of SMC markers including MYH11, CNN1, ACTA2, SM22α. Interestingly, SMCs derived from BAV-NCSCs had significantly decreased in MYH11 and ACTA2 gene expression and impaired contractile property by gel contraction assay compared to SMCs derived from control-NCSCs. However, SMCs from BAV-PMCs had similar level of expression of MYH11 and ACTA2, and strong contractile activity with Carbacol treatment compared to SMCs derived from control PMCs. In conclusion, the iPS model system revealed decreased expression of contractile proteins and impairment of contractility in SMCs derived from NCSCs in BAV patient, but not in the SMCs derived from paraxial mesoderm cells. The high susceptibility of aneurysm in the ascending aorta in patients with BAV might be partly due to embryonic origin of the SMCs.


2020 ◽  
Vol 27 (5) ◽  
pp. 784-797.e11
Author(s):  
Liang Zhang ◽  
John Avery ◽  
Amelia Yin ◽  
Amar M. Singh ◽  
Timothy S. Cliff ◽  
...  

F1000Research ◽  
2015 ◽  
Vol 4 ◽  
pp. 100 ◽  
Author(s):  
Anestis Tsakiridis ◽  
Valerie Wilson

Retrospective clonal analysis in the mouse has demonstrated that the posterior spinal cord neurectoderm and paraxial mesoderm share a common bipotent progenitor. These neuromesodermal progenitors (NMPs) are the source of new axial structures during embryonic rostrocaudal axis elongation and are marked by the simultaneous co-expression of the transcription factors T(Brachyury) (T(Bra)) and Sox2. NMP-like cells have recently been derived from pluripotent stem cells in vitro following combined stimulation of Wnt and fibroblast growth factor (FGF) signaling. Under these conditions the majority of cultures consist of T(Bra)/Sox2 co-expressing cells after 48-72 hours of differentiation. Although the capacity of these cells to generate posterior neural and paraxial mesoderm derivatives has been demonstrated at the population level, it is unknown whether a single in vitro-derived NMP can give rise to both neural and mesodermal cells. Here we demonstrate that T(Bra) positive cells obtained from mouse epiblast stem cells (EpiSCs) after culture in NMP-inducing conditions can generate both neural and mesodermal clones. This finding suggests that, similar to their embryonic counterparts, in vitro-derived NMPs are truly bipotent and can thus be exploited as a model for studying the molecular basis of developmental cell fate decisions.


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

2014 ◽  
Vol 62 (S 01) ◽  
Author(s):  
B. Oberwallner ◽  
A. Brodarac ◽  
P. Anic ◽  
T. Saric ◽  
K. Bieback ◽  
...  

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