ArticleAmerican journal of physiology. Endocrinology and metabolism2013
Activation of the amino acid response modulates lineage specification during differentiation of murine embryonic stem cells.
Article in American journal of physiology. Endocrinology and metabolism, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 12 citations in OpenAlex.
- Regulation of Translation of ATF4 mRNA: A Focus on Translation Initiation Factors and RNA-Binding Proteins.Cells · 2026Review
- Screening and functional verification of potential metabolites for high fertility in sows.Frontiers in nutrition · 2026Article
- Nisin and non-essential amino acids: new perspective in differentiation of neural progenitors from human-induced pluripotent stem cells in vitro.Human cell · 2021Article
- Histone crotonylation promotes mesoendodermal commitment of human embryonic stem cells.Cell stem cell · 2021Article
- Modeling Mammalian Commitment to the Neural Lineage Using Embryos and Embryonic Stem Cells.Frontiers in physiology · 2019Review
- Surviving Stress: Modulation of ATF4-Mediated Stress Responses in Normal and Malignant Cells.Trends in endocrinology and metabolism: TEM · 2017Review
- Influence of Amino Acid Metabolism on Embryonic Stem Cell Function and Differentiation.Advances in nutrition (Bethesda, Md.) · 2016Review
- A novel autoregulatory loop between the Gcn2-Atf4 pathway and (L)-Proline [corrected] metabolism controls stem cell identity.Cell death and differentiation · 2015Article
- Glutamine contributes to maintenance of mouse embryonic stem cell self-renewal through PKC-dependent downregulation of HDAC1 and DNMT1/3a.Cell cycle (Georgetown, Tex.) · 2015Article
- The SLC38 family of sodium-amino acid co-transporters.Pflugers Archiv : European journal of physiology · 2014Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
In somatic cells, a collection of signaling pathways activated by amino acid limitation have been identified and referred to as the amino acid response (AAR). Despite the importance of possible detrimental effects of nutrient limitation during in vitro culture, the AAR has not been investigated in embryonic stem cells (ESC). AAR activation caused the expected increase in transcription factors that mediate specific AAR pathways, as well as the induction of asparagine synthetase, a terminal AAR target gene. Neither AAR activation nor stable knockdown of activating transcription factor (Atf) 4, a transcriptional mediator of the AAR, adversely affected ESC self-renewal or pluripotency. Low-level induction of the AAR over a 12-day period of embryoid body differentiation did alter lineage specification such that the primitive endodermal, visceral endodermal, and endodermal lineages were favored, whereas mesodermal and certain ectodermal lineages were suppressed. Knockdown of Atf4 further enhanced the AAR-induced increase in endodermal formation, suggesting that this phenomenon is mediated by an Atf4-independent mechanism. Collectively, the results indicate that, during differentiation of mouse embryoid bodies in culture, the availability of nutrients, such as amino acids, can influence the formation of specific cell lineages.
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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.