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

Lu, Vivian; Dahan, Perrine; Ahsan, Fasih M.; Patananan, Alexander N.; Roy, Irena J.; Torres, Alejandro; Nguyen, Reginald T; Huang, Dian; Braas, Daniel; Teitell, Michael A.

doi:10.1038/s41422-019-0191-2

Cited by 23 publications

(14 citation statements)

References 16 publications

(20 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We show here that glutamine-free conditions abrogate blood emergence from iPSC-derived HE cells. Previously, glutamine deprivation was also shown to impair iPSC-derived mesoderm formation, which is the precursor germ layer for blood 36 . In contrast, cardiomyocytes, another mesoderm-derived cell type, have been shown to heavily rely on glucose rather than glutamine to fuel OXPHOS during their differentiation from iPSCs 37 .…”

Section: Discussionmentioning

confidence: 99%

Glutamine metabolism regulates endothelial to hematopoietic transition and hematopoietic lineage specification

Oburoglu

Mansell

Woods

2021

Sci Rep

View full text Add to dashboard Cite

During hematopoietic development, definitive hematopoietic cells are derived from hemogenic endothelial (HE) cells through a process known as endothelial to hematopoietic transition (EHT). During EHT, transitioning cells proliferate and undergo progressive changes in gene expression culminating in the new cell identity with corresponding changes in function, phenotype and morphology. However, the metabolic pathways fueling this transition remain unclear. We show here that glutamine is a crucial regulator of EHT and a rate limiting metabolite in the hematopoietic differentiation of HE cells. Intriguingly, different hematopoietic lineages require distinct derivatives of glutamine. While both derivatives, α-ketoglutarate and nucleotides, are required for early erythroid differentiation of HE during glutamine deprivation, lymphoid differentiation relies on α-ketoglutarate alone. Furthermore, treatment of HE cells with α-ketoglutarate in glutamine-free conditions pushes their differentiation towards lymphoid lineages both in vitro and in vivo, following transplantation into NSG mice. Thus, we report an essential role for glutamine metabolism during EHT, regulating both the emergence and the specification of hematopoietic cells through its various derivatives.

show abstract

Section: Discussionmentioning

confidence: 99%

Glutamine metabolism regulates endothelial to hematopoietic transition and hematopoietic lineage specification

Oburoglu

Mansell

Woods

2021

Sci Rep

View full text Add to dashboard Cite

show abstract

“…By contrast, mESCs grown in LIF-containing medium without 2i supplementation are more advanced, with glutamine deprivation causing increased spontaneous differentiation, mainly into trophectoderm (TE) and mesoderm, and decreased pluripotency transcription factor expression (Carey et al, 2015;Ryu et al, 2015). In primed hPSCs, spontaneous differentiation upon glutamine deprivation inhibits mesoderm and promotes ectoderm lineage development, suggesting a lineage-specific requirement for glutamine (Lu et al, 2019). Together, these reports suggest a context-specific glutamine requirement with different PSC differentiation outcomes based on PSC status.…”

Section: Nutrients and Pscs In Contextmentioning

confidence: 99%

Nutrients in the fate of pluripotent stem cells

Roy

Teitell

2021

Cell Metabolism

Self Cite

View full text Add to dashboard Cite

“…In human pluripotent stem cells, as the cells exit pluripotency and enter the initial differentiation phase a metabolic shift to mitochondrial OXP occurs [ 58 , 59 ]. A similar shift occurs as myoblasts fuse differentiate into myotubes [ 60 ].…”

Section: Figure A1mentioning

confidence: 99%

Preliminary Techno-Economic Assessment of Animal Cell-Based Meat

Risner

Fell

et al. 2020

Foods

View full text Add to dashboard Cite

Interest in animal cell-based meat (ACBM) or laboratory-grown meat has been increasing; however, the economic viability of these potential products has not been thoroughly vetted. Recent studies suggest monoclonal antibody production technology can be adapted for the industrialization of ACBM production. This study provides a scenario-based assessment of the projected cost per kilogram of ACBM produced in the United States based on cellular metabolic requirements and process/chemical engineering conventions. A sensitivity analysis of the model identified the nine most influential cost factors for ACBM production out of 67 initial parameters. The results indicate that technological performance will need to approach technical limits for ACBM to achieve profitably as a commodity. However, the model also suggests that low-volume high-value specialty products could be viable based on current technology.

show abstract

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

Cited by 23 publications

References 16 publications

Glutamine metabolism regulates endothelial to hematopoietic transition and hematopoietic lineage specification

Glutamine metabolism regulates endothelial to hematopoietic transition and hematopoietic lineage specification

Nutrients in the fate of pluripotent stem cells

Preliminary Techno-Economic Assessment of Animal Cell-Based Meat

Contact Info

Product

Resources

About