ArticleCell death discovery2022
Mitochondrial homeostasis regulates definitive endoderm differentiation of human pluripotent stem cells.
Article in Cell death discovery, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 54 citations in OpenAlex.
- TGFβ-dependent upregulation of OCIAD2 is essential for epithelial-to-mesenchymal transition during mesendoderm differentiation.Stem cell reports · 2026Article
- TGFβ-activated PDHB promotes mitochondrial pyruvate metabolism and contributes to human endoderm differentiation via ATP-dependent BRG1.Nature communications · 2026Article
- HMGB1 regulates mitochondrial structure and reactive oxygen species balance during the transition from naïve to primed pluripotency.Frontiers in cell and developmental biology · 2026Article
- Mitochondrial development and remodeling occur at pancreatic progenitor stage during induction of stem cell-derived islet organoids.Frontiers in endocrinology · 2026Article
- Mitochondrial dysfunction by glyoxalase 1 deficiency disrupts definitive endoderm and alveolar development of human pluripotent stem cells.Experimental & molecular medicine · 2025Article
- The multifaceted role of mitochondria in cardiac function: insights and approaches.Cell communication and signaling : CCS · 2024Review
- Melatonin-loaded bioactive microspheres accelerate aged bone regeneration by formation of tunneling nanotubes to enhance mitochondrial transfer.Materials today. Bio · 2024Article
- Fasudil and viscosity of gelatin promote hepatic differentiation by regulating organelles in human umbilical cord matrix-mesenchymal stem cells.Stem cell research & therapy · 2024Article
- Low concentrations of saracatinib promote definitive endoderm differentiation through inhibition of FAK-YAP signaling axis.Cell communication and signaling : CCS · 2024Article
- SERS-based long-term mitochondrial pH monitoring during differentiation of human induced pluripotent stem cells to neural progenitor cells.Biomedical optics express · 2024Article
- Metabolic switching, growth kinetics and cell yields in the scalable manufacture of stem cell-derived insulin-producing cells.Stem cell research & therapy · 2024Article
- Phosphorylation stabilized TET1 acts as an oncoprotein and therapeutic target in B cell acute lymphoblastic leukemia.Science translational medicine · 2023Article
- Mitochondrial regulation in human pluripotent stem cells during reprogramming and β cell differentiation.Frontiers in endocrinology · 2023Review
- Cardiolipin externalization mediates prion protein (PrP) peptide 106-126-associated mitophagy and mitochondrial dysfunction.Frontiers in molecular neuroscience · 2023Article
- Tunneling nanotubes and mesenchymal stem cells: New insights into the role of melatonin in neuronal recovery.Journal of pineal research · 2022Review
- Stepwise differentiation of functional pancreatic β cells from human pluripotent stem cells.Cell regeneration (London, England) · 2022Review
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
Cellular organelles play fundamental roles in almost all cell behaviors. Mitochondria have been reported to be functionally linked to various biological processes, including reprogramming and pluripotency maintenance. However, very little about the role of mitochondria has been revealed in human early development and lineage specification. Here, we reported the characteristics and function of mitochondria during human definitive endoderm differentiation. Using a well-established differentiation system, we first investigated the change of mitochondrial morphology by comparing undifferentiated pluripotent stem cells, the intermediate mesendoderm cells, and differentiated endoderm cells, and found that mitochondria were gradually elongated and matured along differentiation. We further analyzed the expression pattern of mitochondria-related genes by RNA-seq, indicating that mitochondria became active during differentiation. Supporting this notion, the production of adenosine triphosphate (ATP) and reactive oxygen species (ROS) was increased as well. Functionally, we utilized chemicals and genome editing techniques, which could interfere with mitochondrial homeostasis, to determine the role of mitochondria in human endoderm differentiation. Treatment with mitochondrial inhibitors, or genetic depletion of mitochondrial transcription factor A (TFAM), significantly reduced the differentiation efficiency of definitive endoderm. In addition, the defect in endoderm differentiation due to dysfunctional mitochondria could be restored to some extent by the addition of ATP. Moreover, the clearance of excessive ROS due to dysfunctional mitochondria by N-acetylcysteine (NAC) improved the differentiation as well. We further found that ATP and NAC could partially replace the growth factor activin A for definitive endoderm differentiation. Our study illustrates the essential role of mitochondria during human endoderm differentiation through providing ATP and regulating ROS levels, which may provide new insight for metabolic regulation of cell fate determination.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.