scholarly journals Defining early hematopoietic‐fated primitive streak specification of human pluripotent stem cells by the orchestrated balance of Wnt, activin, and BMP signaling

2019 ◽  
Vol 234 (9) ◽  
pp. 16136-16147
Author(s):  
Jun Shen ◽  
Cuicui Lyu ◽  
Yaoyao Zhu ◽  
Zicen Feng ◽  
Shuo Zhang ◽  
...  
2019 ◽  
Vol 24 (5) ◽  
pp. 829 ◽  
Author(s):  
Jorge O. Múnera ◽  
Nambirajan Sundaram ◽  
Scott A. Rankin ◽  
David Hill ◽  
Carey Watson ◽  
...  

2017 ◽  
Vol 21 (1) ◽  
pp. 51-64.e6 ◽  
Author(s):  
Jorge O. Múnera ◽  
Nambirajan Sundaram ◽  
Scott A. Rankin ◽  
David Hill ◽  
Carey Watson ◽  
...  

2018 ◽  
Vol 11 (6) ◽  
pp. 1357-1364 ◽  
Author(s):  
Hui-Ting Hsu ◽  
Conchi Estarás ◽  
Ling Huang ◽  
Katherine A. Jones

2019 ◽  
Author(s):  
Loukia Yiangou ◽  
Rodrigo A. Grandy ◽  
Sanjay Sinha ◽  
Ludovic Vallier

ABSTRACTMesoderm is one of the three germ layers produced during gastrulation from which muscle, bones, kidneys and the cardiovascular system originate. Understanding the mechanisms controlling mesoderm specification could be essential for a diversity of applications, including the development of regenerative medicine therapies against diseases affecting these tissues. Here, we use human pluripotent stem cells (hPSCs) to investigate the role of cell cycle in mesoderm formation. For that, proteins controlling G1 and G2/M cell cycle phases were inhibited during differentiation of hPSCs into lateral plate, cardiac and presomitic mesoderm using small molecules or by conditional knock down. These loss of function experiments revealed that CDKs and pRb phosphorylation are necessary for efficient mesoderm formation in a context-dependent manner. Further investigations showed that inhibition of the G2/M regulator CDK1 decreases BMP signaling activity specifically during lateral plate mesoderm formation while reducing FGF/ERK1/2 activity in all mesoderm subtypes. Taken together, our findings reveal that cell cycle regulators direct mesoderm formation by controlling the activity of key developmental pathways.


eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
John Aach ◽  
Jeantine Lunshof ◽  
Eswar Iyer ◽  
George M Church

The "14-day rule" for embryo research stipulates that experiments with intact human embryos must not allow them to develop beyond 14 days or the appearance of the primitive streak. However, recent experiments showing that suitably cultured human pluripotent stem cells can self-organize and recapitulate embryonic features have highlighted difficulties with the 14-day rule and led to calls for its reassessment. Here we argue that these and related experiments raise more foundational issues that cannot be fixed by adjusting the 14-day rule, because the framework underlying the rule cannot adequately describe the ways by which synthetic human entities with embryo-like features (SHEEFs) might develop morally concerning features through altered forms of development. We propose that limits on research with SHEEFs be based as directly as possible on the generation of such features, and recommend that the research and bioethics communities lead a wide-ranging inquiry aimed at mapping out solutions to the ethical problems raised by them.


Pneumologie ◽  
2015 ◽  
Vol 69 (07) ◽  
Author(s):  
S Ulrich ◽  
S Weinreich ◽  
R Haller ◽  
S Menke ◽  
R Olmer ◽  
...  

Diabetes ◽  
2019 ◽  
Vol 68 (Supplement 1) ◽  
pp. 326-LB
Author(s):  
LARRY SAI WENG LOO ◽  
ADRIAN TEO ◽  
SOUMITA GHOSH ◽  
ANDREAS ALVIN PURNOMO SOETEDJO ◽  
LINH NGUYEN ◽  
...  

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