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Mitochondrial metabolism and glutamine are essential for mesoderm differentiation of human pluripotent stem cells

mitochondria glutamine mesoderm ipsc

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#1 Engadin

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Posted 12 June 2019 - 08:33 PM


BEHIND PAYWALL

 

 

 

S O U R C E : Nature


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#2 Heisok

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Posted 12 June 2019 - 10:03 PM

I think that the Nature article is based on the same work discussed in the Journal of Biological Chemistry. Based on the same studies, and sharing references. The JBC goes deep. https://www.ncbi.nlm...les/PMC6462533/

 

"Abstract"

Pluripotent stem cells (PSCs) are highly proliferative cells characterized by robust metabolic demands to power rapid division. For many years considered a passive component or “passenger” of cell-fate determination, cell metabolism is now starting to take center stage as a driver of cell fate outcomes. This review provides an update and analysis of our current understanding of PSC metabolism and its role in self-renewal, differentiation, and somatic cell reprogramming to pluripotency. Moreover, we present evidence on the active roles metabolism plays in shaping the epigenome to influence patterns of gene expression that may model key features of early embryonic development.

 

Conclusions:

"Accumulating evidence illustrates the influence of metabolism on differentiation plasticity by regulating the epigenetic machinery. Our current understanding provides a foundation for further investigations into links between environmental stimuli and subsequent metabolic adaptations that orchestrate epigenome remodeling events, which ultimately drive cell fate. A key open question is what recruits epigenome remodelers, co-factors, and substrates to specific loci to influence patterns of pluripotent and somatic cell gene expression. Here, we suggest that HBP may have a role by acting at crucial nodes connecting metabolism and epigenome remodeling. Answers to fundamental questions raised here will provide a deeper basis for generating safe and accessible PSC-derived cells for use in regenerative medicine, disease modeling, and drug screening applications in the future."

 

"National Institutes of Health Grants CA90571, GM073981, CA18589, and GM114188 and Air Force Office of Scientific Research Grant FA9550-15-1-0406 (to M. A. T.)."

 


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