As the saying goes, a healthy person has a thousand wishes, a sick person has only one. What if science could grant this wish at will?
Human pluripotent stem cells give humans the superpower to regenerate cells (or organs) and reverse aging. Cell regeneration techniques are probably going to be at the center of research in the coming decade. The size of Jeff Bezos's recent investment in Altos Labs probably gets us an idea of the gravity of interest in this domain.
Image credit: Piqsels, free public domain licence
Research efforrs in this field are also very active. In one of the latest articles, L E Wadkin, S Orozco-Fuentes, I Neganova, M Lako, N G Parker, and A Shukurov have discussed a mathematical model for the regulation of pluripotency in human stem cells. This research paper forms the basis of the following text.
Importance of this research
The researchers have provided a non-invasive mathematical model to explore, characterize and replicate the regulation of pluripotency and the consequences on cell fate. The mathematical model provides predictability for human pluripotent stem cells (hPSCs) development with tremendous applications in regenerative medicine, drug discovery, and personalized medicine.
Experimental Setup
The researchers used Purvis Lab of the University of North Carolina, School of Medicine for the experiment. The cell colony starts with 30 cells & Images were taken every 5 minutes till the colony grew to 463 cells in 68 hours, with 1274 cell cycles elapsed. After 40 hours, the hESCs were treated with bone morphogenetic protein 4 (BMP4) to induce their differentiation towards distinct cell fates.
Experiment Procedure
Cell fate refers to the decision of the cell to either remain pluripotent or to differentiate itself. The expression levels of CDX2 were quantified at 68 hours to classify the cells as either self-renewing (pluripotent) or differentiated. Then, the cell population was traced back in time, spanning multiple cell divisions, with each earlier cell labeled according to this pro-fate
Experiment Results
The experimental results and the simulated results were shown graphically by the team in the research paper. Summary of the observed phenomena and the associated model for describing the behavior are as below:
Image credit: arXiv:2102.12860 [q-bio.SC]
Conclusion
In the words of the researchers,
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. This mathematical framework for describing intra-cellular OCT4 regulation can be extended to other transcription factors and developed into sophisticated predictive models.
Source: L E Wadkin, S Orozco-Fuentes, I Neganova, M Lako, N G Parker and A Shukurov's “A mathematical modelling framework for the regulation of intra-cellular OCT4 in human pluripotent stem cells“