Statistical and mathematical modeling of spatiotemporal dynamics of stem cells

TL;DR

This paper reviews statistical and mathematical modeling techniques used to analyze and simulate the spatiotemporal dynamics of hematopoietic stem and progenitor cells within their microenvironment, aiding understanding of normal and abnormal hematopoiesis.

Contribution

It provides an overview of statistical analysis methods and cell-based modeling formalisms for studying stem cell behavior in their niche.

Findings

Quantitative methods for analyzing cell spatial distribution and motility.

Cell-based modeling approaches for simulating emergent multicellular behavior.

A workflow integrating statistical analysis and modeling for hematopoietic stem cell research.

Abstract

Statistical and mathematical modeling are crucial to describe, interpret, compare and predict the behavior of complex biological systems including the organization of hematopoietic stem and progenitor cells in the bone marrow environment. The current prominence of high-resolution and live-cell imaging data provides an unprecedented opportunity to study the spatiotemporal dynamics of these cells within their stem cell niche and learn more about aberrant, but also unperturbed, normal hematopoiesis. However, this requires careful quantitative statistical analysis of the spatial and temporal behavior of cells and the interaction with their microenvironment. Moreover, such quantification is a prerequisite for the construction of hypothesis-driven mathematical models that can provide mechanistic explanations by generating spatiotemporal dynamics that can be directly compared to experimental observations. Here, we provide a brief overview of statistical methods in analyzing spatial distribution of cells, cell motility, cell shapes and cellular genealogies. We also describe cell- based modeling formalisms that allow researchers to simulate emergent behavior in a multicellular system based on a set of hypothesized mechanisms. Together, these methods provide a quantitative workflow for the analytic and synthetic study of the spatiotemporal behavior of hematopoietic stem and progenitor cells.