Regulation of stem cell dynamics through volume exclusion

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

The maintenance and regeneration of adult tissues rely on the self-renewal of stem cells. Regeneration without over-proliferation requires precise regulation
of the stem cell proliferation and differentiation rates. The nature of such regulatory mechanisms in different tissues, and how to incorporate them
in models of stem cell population dynamics, is incompletely understood. The critical birth-death (CBD) process is widely used to model stem cell populations, capturing key phenomena, such as scaling laws in clone size distributions. However, the CBD process neglects regulatory mechanisms. Here, we propose the birth-death process with volume exclusion (vBD), a variation of the birth-death process that considers crowding effects, such as may arise due to limited space in a stem cell niche. While the deterministic rate equations predict a single nontrivial attracting steady state, the master equation predicts extinction and transient distributions of stem cell numbers with three possible behaviours:
long-lived quasi-steady state (QSS), and short-lived bimodal or unimodal distributions. In all cases, we approximate solutions to the vBD master equation
using a renormalized system-size expansion, QSS approximation and the Wentzel–Kramers–Brillouin method. Our study suggests that the size distribution
of a stem cell population bears signatures that are useful to detect negative feedback mediated via volume exclusion.
Original languageEnglish
Article number20220376
Number of pages22
JournalProceedings of the royal society of london series a-Mathematical and physical sciences
Volume478
DOIs
Publication statusPublished - 26 Oct 2022

Keywords / Materials (for Non-textual outputs)

  • stem cells
  • volume exclusion
  • master equation
  • renormalized system-size expansion
  • transient bimodality
  • regulation

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