Spatial patterning of early neural differentiation in pluripotent cells
Early neural differentiation in pluripotent cells is the shift from a cell able to make nearly every lineage to a neural progenitor. Oct4 and Sox2 mark the shift. Both are present in pluripotent embryonic stem cells, and Sox2 alone is associated with neural ectoderm3. Glen and colleagues reported that in a colony the loss of Oct4 is patterned in space4.
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- 2012, Pai VP, Vandenberg LN…
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- Dynamic intercellular transport modulates the…, 2018
- In the library
- 64 passages in 12 works
- Rewritten
- 2026-10-23
Restriction of potency
Pillozzi and Becchetti (2012) describe development as a progressive restriction of differentiation potency, in which primordial pluripotent cells can self-renew and give rise to all lineages except the extraembryonic ones1. They add that it is uncertain whether the range of outcomes in a stem cell population depends on extrinsic regulation or on the existence of heterogeneous stem cell populations1. Rink (2013) stresses the transcriptional side of pluripotency. In induced pluripotent stem cell formation, Oct4 and Sox2 usually have to be expressed, and through mutual binding sites in their promoters they set up self-maintaining transcriptional networks2.
Patterning in colonies
Glen, McDevitt and Kemp (2018) treated monolayers of mouse embryonic stem cell colonies with retinoic acid for 72 hours. They chose a flat monolayer because it minimizes the build-up of paracrine factors seen in aggregates. This lets heterogeneity caused by intercellular mechanisms be studied with less confounding3. Differentiation was followed by Oct4 and Sox2. They saw a transient, patterned loss of Oct4 while Sox2 was maintained4. About 70% of cells (±4%) became Oct4-negative, Sox2-positive neural progenitors within 48 hours5. Withdrawing LIF instead lowered both factors, which is associated with endoderm and mesoderm5.
Electrical cues
O'Hara-Wright, Mobini and Gonzalez-Cordero (2022) review work on electrical stimulation. They report that Yamada and colleagues (2007) gave the first evidence that mild stimulation of mouse embryonic stem cells raised their tendency toward neural differentiation6. They also state that studies of organoids derived from pluripotent stem cells have not considered bioelectric cues in the morphogenesis of the nervous system7.
Pluripotency factors in cancer
Two 2026 papers carry the same factors into cancer. Desoyer and colleagues report that cancer stem cells have more depolarised membrane potentials than non-malignant stem cells. They link this state to sustained OCT4, SOX2 and NANOG expression and to stemness8. Acharya and colleagues note that OCT4 and NANOG are co-expressed with cancer stem cell markers in oral squamous cell carcinoma. They suggest that embryonic pluripotency circuits are reactivated in the malignant state9. These accounts concern cancer, not neural differentiation.
During development, a progressive restriction in differentiation potency occurs, with primordial pluripotent cells being able to yield other stem cells (self-renewal)
Pillozzi S, Becchetti A, 2012 · Ion channels in hematopoietic and mesenchymal stem cells · open at passage 1IPS cell formation usually requires expression of the POU-domain transcription factor Oct4 and Sox2, which via mutual binding sites in their promoters establish self-maintaining transcriptional networks
Rink JC, 2013 · Stem cell systems and regeneration in planaria · open at passage 22The Oct4 + Sox2 + state has been well characterized to reflect the pluripotent state of ESCs, whereas Sox2 expression alone (in the absence of Oct4) is associated with a neural ectoderm fate
Glen CM, McDevitt TC, Kemp ML, 2018 · Dynamic intercellular transport modulates the spatial patterning of… · open at passage 6As differentiation proceeded, a transient, patterned loss of Oct4 was observed while Sox2 expression was maintained, as expected for neural progenitors (Fig. 1a).
Glen CM, McDevitt TC, Kemp ML, 2018 · Dynamic intercellular transport modulates the spatial patterning of… · open at passage 7The majority of the cell population (70 ± 4%) assumed an Oct4-Sox2 + neural progenitor state within 48 h of RA treatment.
Glen CM, McDevitt TC, Kemp ML, 2018 · Dynamic intercellular transport modulates the spatial patterning of… · open at passage 7Yamada et al. (2007) described the first study showing mild electrical stimulation of mouse ESCs resulted in increased propensity for neural differentiation.
O'Hara-Wright M, Mobini S, Gonzalez-Cordero A, 2022 · Bioelectric Potential in Next-Generation Organoids: Electrical Stimulation to… · open at passage 30Yet studies of PSC-derived CNS organoids have not considered the role of bioelectric cues in CNS morphogenesis and attempted to recapitulate these in the dish.
O'Hara-Wright M, Mobini S, Gonzalez-Cordero A, 2022 · Bioelectric Potential in Next-Generation Organoids: Electrical Stimulation to… · open at passage 16This depolarised bioelectric state is closely associated with the maintenance of stemness, including the sustained expression of transcription factors such as OCT4, SOX2 and NANOG
Desoyer C, Šupe R, Ghorbanpour S, Goswami D, Khalaj M…, 2026 · Cancer: A bioelectric disease? · open at passage 49Co-expression of OCT4 and NANOG with CSC markers in OSCC suggests that embryonic pluripotency GRN modules are reactivated as part of the malignant attractor programme
Acharya SK, Ngeow WC, Hariri F, Liew FF, Choon YF, 2026 · A Convergence Model of Bioelectric, Gap Junctional, and Hippo-YAP Signalling in… · open at passage 13