Hematopoietic stem cells (HSCs) can undergo both symmetric and asymmetric cell divisions. During their stay in the fetal liver, symmetric expansion of HSCs is very fast compared to their proliferation in the adult bone marrow. This makes the fetal liver an interesting tissue to study for medical purposes (e.g., identifying the essential conditions to rapidly expand HSCs in vitro). The behavior of stem cells is strongly affected by their chemical and mechanical niche. Locally produced molecular factors, extracellular matrix and surrounding cells all regulate stem cell fate. Through mechanotransduction, cells are able to convert mechanical stimuli into chemical activity. Additionally, various molecular cues trigger cells by binding with their membrane receptors and initiate a cascade of intracellular reactions. Via transcription factors, these pathways may ultimately cause differential gene expression. Regarding the small numbers of key molecules and the microscopic scale at which molecular reactions take place, the influence of stochasticity may not be neglected. More specifically, cellular heterogeneity is observed in gene expression patterns between cells of the same isogenic population (e.g., differentiation of HSCs into distinct hematopoietic lineages, symmetric or asymmetric HSC divisions, etc.). The principal goal of this study is the investigation and particle-based quantitative modeling of the crucial intracellular pathways of HSCs during the fetal liver stage, of chemical and physical extracellular keys influencing HSC behavior, and of how stochasticity plays a role in these processes.
