ArticleStem cells (Dayton, Ohio)2013
TGF-β-superfamily signaling regulates embryonic stem cell heterogeneity: self-renewal as a dynamic and regulated equilibrium.
Article in Stem cells (Dayton, Ohio), 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 51 citations in OpenAlex.
- TGFβ family signaling in human stem cell self-renewal and differentiation.Cell regeneration (London, England) · 2024Review
- Learning Towards Maturation of Defined Feeder-free Pluripotency Culture Systems: Lessons from Conventional Feeder-based Systems.Stem cell reviews and reports · 2024Review
- The transcription factor EBF1 non-cell-autonomously regulates cardiac growth and differentiation.Development (Cambridge, England) · 2023Article
- Heterogeneity affects the differentiation potential of dental follicle stem cells through the TGF-β signaling pathway.Bioengineered · 2021Article
- Derivation of stable embryonic stem cell-like, but transcriptionally heterogenous, induced pluripotent stem cells from non-permissive mouse strains.Mammalian genome : official journal of the International Mammalian Genome Society · 2020Article
- Dynamics of Phenotypic Heterogeneity Associated with EMT and Stemness during Cancer ProgressionJournal of clinical medicine · 2019Review
- Article
- Id1 Stabilizes Epiblast Identity by Sensing Delays in Nodal Activation and Adjusting the Timing of Differentiation.Developmental cell · 2019Article
- Short Term Development and Fate of MGE-Like Neural Progenitor Cells in Jaundiced and Non-Jaundiced Rat Brain.Cell transplantation · 2018Article
- Article
- Nanog Dynamics in Mouse Embryonic Stem Cells: Results from Systems Biology Approaches.Stem cells international · 2017Review
- Characterization of microRNAs expression profiles in human dental-derived pluripotent stem cells.PloS one · 2017Article
- Gene expression variability in mammalian embryonic stem cells using single cell RNA-seq data.Computational biology and chemistry · 2016Article
- The pituitary TGFβ1 system as a novel target for the treatment of resistant prolactinomas.The Journal of endocrinology · 2016Review
- BMP-SMAD Signaling Regulates Lineage Priming, but Is Dispensable for Self-Renewal in Mouse Embryonic Stem Cells.Stem cell reports · 2016Article
- Integration of Signaling Pathways with the Epigenetic Machinery in the Maintenance of Stem Cells.Stem cells international · 2016Review
- The availability of the embryonic TGF-β protein Nodal is dynamically regulated during glioblastoma multiforme tumorigenesis.Cancer cell international · 2016Article
- Cell Cycle-Driven Heterogeneity: On the Road to Demystifying the Transitions between "Poised" and "Restricted" Pluripotent Cell States.Stem cells international · 2015Review
- Endogenous WNT signaling regulates hPSC-derived neural progenitor cell heterogeneity and specifies their regional identity.Stem cell reports · 2014Article
- Autocrine FGF feedback can establish distinct states of Nanog expression in pluripotent stem cells: a computational analysis.BMC systems biology · 2014Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Embryonic stem cells dynamically fluctuate between phenotypic states, as defined by expression levels of genes such as Nanog, while remaining pluripotent. The dynamic phenotype of stem cells is in part determined by gene expression control and dictated by various signaling pathways and transcriptional regulators. We sought to define the activities of two TGF-β-related signaling pathways, bone morphogenetic protein (BMP) and Nodal signaling, in modulating mouse embryonic stem (ES) cell heterogeneity in undifferentiated culture conditions. Both BMP and Nodal signaling pathways were seen to be active in distinct Nanog subpopulations, with subtle quantitative differences in activity. Pharmacological and genetic modulation of BMP or Nodal signaling strongly influenced the heterogeneous state of undifferentiated ES cells, as assessed by dynamic expression of Nanog reporters. Inhibition of Nodal signaling enhanced BMP activity, which through the downstream target Id factors, enhanced the capacity of ES cells to remain in the Nanog-high epigenetic state. The combined inhibition of Nodal and BMP signaling resulted in the accumulation of Nanog-negative cells, even in the presence of LIF, uncovering a shared role for BMP and Nodal signaling in maintaining Nanog expression and repression of differentiation. These results demonstrate a complex requirement for both arms of TGF-β-related signaling to influence the dynamic cellular phenotype of undifferentiated ES cells in serum-based media, and that differing subpopulations of ES cells in heterogeneous culture have distinct responses to these signaling pathways. Several pathways, including BMP, Nodal, and FGF signaling, have important regulatory function in defining the steady-state distribution of heterogeneity of stem cells.
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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 Socratic graph.