OCT4 expression in human embryonic stem cells: spatio-temporal dynamics and fate transitions

Wadkin, Laura E; Orozco-Fuentes, Sirio; Neganova, Irina; Lako, Majlinda; Barrio, Rafael A.; Baggaley, Andrew W.; Parker, N. G.; Shukurov, Anvar

doi:10.1088/1478-3975/abd22b

Cited by 7 publications

(29 citation statements)

References 88 publications

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“…[ 14 ] and our previous analysis of this data in Ref. [ 29 ] to guide model development. Although focused on one experiment, the mathematical framework outlined here is easily adaptable to other experimental results.…”

Section: Experimental Oct4 Fluctuationsmentioning

confidence: 99%

“…[ 14 ] and Ref. [ 29 ] to illustrate the applicability of such models to PTF regulation. Here we summarise the experiment and main features of the data to be described by a mathematical model.…”

Section: Experimental Oct4 Fluctuationsmentioning

confidence: 99%

“…A detailed analysis of the experimental data is provided in Ref. [ 29 ]. For simplicity, and due to the distinct behavioural differences identified pre- and post-differentiation, we first consider modelling the temporal behaviour pre-BMP4 before moving on to the effect of cell differentiation.…”

Section: Experimental Oct4 Fluctuationsmentioning

confidence: 99%

“…Although the OCT4 dynamics will be affected by many external factors and the remainder of the PTF network, there are benefits to considering each PTF in isolation as the crucial first step; firstly, this simplifies the model development process, allowing each element to be explored in a systematic way and secondly, the results provide a basis for comparison to the other PTFs (e.g., NANOG and SOX2) from similar experiments. Similarly, although interesting spatial patterning effects are seen in OCT4 [ 29 ], we will consider only the intra-cellular OCT4 behaviour through time. These simpler models can be used to describe the stochastic nature of PTF regulation on shorter time scales and explore the effects of each PTF on cell fate, before their development into coupled models of the entire pluripotency regulatory network.…”

Section: Introductionmentioning

confidence: 99%

“…[ 14 ] and the additional quantitative analysis of this dataset from Ref. [ 29 ]. The framework discussed can be applied in future to other experimental datasets.…”

Section: Introductionmentioning

confidence: 99%

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A mathematical modelling framework for the regulation of intra-cellular OCT4 in human pluripotent stem cells

et al. 2021

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Human pluripotent stem cells (hPSCs) have the potential to differentiate into all cell types, a property known as pluripotency. A deeper understanding of how pluripotency is regulated is required to assist in controlling pluripotency and differentiation trajectories experimentally. Mathematical modelling provides a non-invasive tool through which to explore, characterise and replicate the regulation of pluripotency and the consequences on cell fate. Here we use experimental data of the expression of the pluripotency transcription factor OCT4 in a growing hPSC colony to develop and evaluate mathematical models for temporal pluripotency regulation. We consider fractional Brownian motion and the stochastic logistic equation and explore the effects of both additive and multiplicative noise. We illustrate the use of time-dependent carrying capacities and the introduction of Allee effects to the stochastic logistic equation to describe cell differentiation. We conclude both methods adequately capture the decline in OCT4 upon differentiation, but the Allee effect model has the advantage of allowing differentiation to occur stochastically in a sub-set of cells. This mathematical framework for describing intra-cellular OCT4 regulation can be extended to other transcription factors and developed into predictive models.

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Section: Experimental Oct4 Fluctuationsmentioning

confidence: 99%

Section: Experimental Oct4 Fluctuationsmentioning

confidence: 99%

Section: Experimental Oct4 Fluctuationsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

“…[ 14 ] and the additional quantitative analysis of this dataset from Ref. [ 29 ]. The framework discussed can be applied in future to other experimental datasets.…”

Section: Introductionmentioning

confidence: 99%

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A mathematical modelling framework for the regulation of intra-cellular OCT4 in human pluripotent stem cells

et al. 2021

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Human Stem Cells for Ophthalmology: Recent Advances in Diagnostic Image Analysis and Computational Modelling

Wadkin,

Makarenko,

Parker

et al. 2023

Curr Stem Cell Rep

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Purpose of Review To explore the advances and future research directions in image analysis and computational modelling of human stem cells (hSCs) for ophthalmological applications. Recent Findings hSCs hold great potential in ocular regenerative medicine due to their application in cell-based therapies and in disease modelling and drug discovery using state-of-the-art 2D and 3D organoid models. However, a deeper characterisation of their complex, multi-scale properties is required to optimise their translation to clinical practice. Image analysis combined with computational modelling is a powerful tool to explore mechanisms of hSC behaviour and aid clinical diagnosis and therapy. Summary Many computational models draw on a variety of techniques, often blending continuum and discrete approaches, and have been used to describe cell differentiation and self-organisation. Machine learning tools are having a significant impact in model development and improving image classification processes for clinical diagnosis and treatment and will be the focus of much future research.

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Culture of leukocyte-derived cells from human peripheral blood: Increased expression of pluripotent genes OCT4, NANOG, SOX2, self-renewal gene TERT and plasticity

et al. 2023

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There are few stem cells in human peripheral blood (PB). Increasing the population and plasticity of stem cells in PB and applying it to regenerative medicine require suitable culture methods. In this study, leukocyte populations 250 mL of PB were collected using a blood separator before that were cultured in optimal cell culture medium for 4 to 7 days. After culturing, stemness characteristics were analyzed, and red blood cells were removed from the cultured cells. In our results, stemness markers of the leukocyte populations Sca-1 + CD45 + , CD117 + CD45 + , and very small embryonic-like stem cells CD34 + Lin − CD45 − and CXCR4 + Lin − CD45 − were significantly increased. Furthermore, the expression of stem cell genes OCT4 (POU5F1), NANOG, SOX2, and the self-renewal gene TERT was analyzed by quantitative real-time polymerase chain reaction in these cells, and it showed a significant increase. These cells could be candidates for multi-potential cells and were further induced using transdifferentiation culture methods. These cells showed multiple differentiation potentials for osteocytes, nerve cells, cardiomyocytes, and hepatocytes. These results indicate that appropriate culture methods can be applied to increase expression of pluripotent genes and plasticity. Leukocytes of human PB can be induced to trans-differentiate into pluripotent potential cells, which will be an important breakthrough in regenerative medicine.

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OCT4 expression in human embryonic stem cells: spatio-temporal dynamics and fate transitions

Abstract: Anvar (2021) OCT4 expression in human embryonic stem cells: spatio-temporal dynamics and fate transitions. Physical Biology, 18 (2). 026003.

Cited by 7 publications

References 88 publications

A mathematical modelling framework for the regulation of intra-cellular OCT4 in human pluripotent stem cells

A mathematical modelling framework for the regulation of intra-cellular OCT4 in human pluripotent stem cells

Human Stem Cells for Ophthalmology: Recent Advances in Diagnostic Image Analysis and Computational Modelling

Culture of leukocyte-derived cells from human peripheral blood: Increased expression of pluripotent genes OCT4, NANOG, SOX2, self-renewal gene TERT and plasticity

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