Section: New Results

Physiology

A multiscale modeling approach for the regulation of the cell cycle by the circadian clock

We present in [18] a multiscale mathematical model for the regulation of the cell cycle by the circadian clock. Biologically, the model describes the proliferation of a population of heterogeneous cells connected to each other. The model consists of a high dimensional transport equation structured by molecular contents of the cell cycle-circadian clock coupled oscillator. We propose a computational method for resolution adapted from the concept of particle methods. We study the impact of molecular dynamics on cell proliferation and show an example where discordance of division rhythms between population and single cell levels is observed. This highlights the importance of multiscale modeling where such results cannot be inferred from considering solely one biological level.

The lifespan and turnover of microglia in the human brain

The hematopoietic system seeds the CNS with microglial progenitor cells during the fetal period, but the subsequent cell generation dynamics and maintenance of this population have been poorly understood. We report in [25] that microglia, unlike most other hematopoietic lineages, renew slowly at a median rate of $28\%$ per year, and some microglia last for more than two decades. Furthermore, we find no evidence for the existence of a substantial population of quiescent long-lived cells, meaning that the microglia population in the human brain is sustained by continuous slow turnover throughout adult life.

Impact of fat mass and distribution on lipid turnover in human adipose tissue

Differences in white adipose tissue (WAT) lipid turnover between the visceral (vWAT) and subcutaneous (sWAT) depots may cause metabolic complications in obesity. In [26], we compare triglyceride age and, thereby, triglyceride turnover in vWAT and sWAT biopsies from 346 individuals and find that subcutaneous triglyceride age and storage capacity are increased in overweight or obese individuals. Visceral triglyceride age is only increased in excessively obese individuals and associated with a lower lipid removal capacity. Thus, although triglyceride storage capacity in sWAT is higher than in vWAT, the former plateaus at substantially lower levels of excess WAT mass than vWAT. In individuals with central or visceral obesity, lipid turnover is selectively increased in vWAT. Obese individuals classified as 'metabolically unhealthy' (according to ATPIII criteria) who have small subcutaneous adipocytes exhibit reduced triglyceride turnover. We conclude that excess WAT results in depot-specific differences in lipid turnover and increased turnover in vWAT and/or decreased turnover in sWAT may result in metabolic complications of overweight or obesity.