Journal
JOURNAL OF THEORETICAL BIOLOGY
Volume 577, Issue -, Pages -Publisher
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.jtbi.2023.111664
Keywords
Stem cell differentiation; Epigenetic state; Waddington landscape; Cell reprogramming; Multi-scale model
Categories
Ask authors/readers for more resources
Maintaining tissue homeostasis requires appropriate regulation of stem cell differentiation. Random inheritance of epigenetic states plays a pivotal role in stem cell differentiation. This computational model provides valuable insights into the intricate mechanism governing stem cell differentiation and cell reprogramming, offering a promising path for enhancing the field of regenerative medicine.
Maintaining tissue homeostasis requires appropriate regulation of stem cell differentiation. The Waddington landscape posits that gene circuits in a cell form a potential landscape of different cell types, wherein cells follow attractors of the probability landscape to develop into distinct cell types. However, how adult stem cells achieve a delicate balance between self-renewal and differentiation remains unclear. We propose that random inheritance of epigenetic states plays a pivotal role in stem cell differentiation and present a hybrid model of stem cell differentiation induced by epigenetic modifications. Our comprehensive model integrates gene regulation networks, epigenetic state inheritance, and cell regeneration, encompassing multi -scale dynamics ranging from transcription regulation to cell population. Through model simulations, we demonstrate that random inheritance of epigenetic states during cell divisions can spontaneously induce cell differentiation, dedifferentiation, and transdifferentiation. Furthermore, we investigate the influences of interfering with epigenetic modifications and introducing additional transcription factors on the probabilities of dedifferentiation and transdifferentiation, revealing the underlying mechanism of cell reprogramming. This in silico model provides valuable insights into the intricate mechanism governing stem cell differentiation and cell reprogramming and offers a promising path to enhance the field of regenerative medicine.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available