Concise Review: Stem Cell Population Biology: Insights from Hematopoiesis

Abstract

Stem cells are fundamental to human life and offer great therapeutic potential, yet their biology remains incompletely-or in cases even poorly-understood. The field of stem cell biology has grown substantially in recent years due to a combination of experimental and theoretical contributions: the experimental branch of this work provides data in an ever-increasing number of dimensions, while the theoretical branch seeks to determine suitable models of the fundamental stem cell processes that these data describe. The application of population dynamics to biology is amongst the oldest applications of mathematics to biology, and the population dynamics perspective continues to offer much today. Here we describe the impact that such a perspective has made in the field of stem cell biology. Using hematopoietic stem cells as our model system, we discuss the approaches that have been used to study their key properties, such as capacity for self-renewal, differentiation, and cell fate lineage choice. We will also discuss the relevance of population dynamics in models of stem cells and cancer, where competition naturally emerges as an influential factor on the temporal evolution of cell populations. STEM CELLS 2017;35:80-88 SIGNIFICANCE STATEMENTAdult stem cells engage in complex interactions with their environment and progeny; these are believed to maintain their stemness. Here we put these observations into a population biology framework which allows us to take ideas from ecology and shed light on the dynamics within the stem cell niche. Using the particular example of hematopoietic stem cells, we show that this perspective helps to understand stem cell dynamics both in cases of health and disease.

The recent advances in the mathematical modelling of human pluripotent stem cells

“…Population models have been used to understand the process by which blood cells are formed [ 22 ], cancer tumours grow [ 85 ] and the impact of hPSC colony growth on clonality [ 86 ]. Early population dynamics models for stem cells were based on stochastic birth–death processes [ 17 ] involving systems of ordinary differential equations [ 87 ].…”

“…Similarly, mathematical models are a powerful tool to further our understanding of hPSC behaviours and optimise crucial experiments. The first mathematical model of stem cells, a stochastic model of cell fate decisions [17], has since been extended to include many other aspects of cell behaviour [18,19,20,21,22]. In particular, when such mathematical models are rigorously underpinned and validated on experimental observations, the reciprocal benefit for experimentation can be profound: an example is the development of an experimentally-rained model of hiPSC programming, which led in turn to strategies for marked improvements in reprogramming efficiency [23].…”

Understanding Hematological Toxicities Using Mathematical Modeling

“…Hematopoiesis modeling has been very prolific (see Refs. for reviews on this topic), and all models of whole hematopoiesis include a common set of essential features: 1) stemness (i.e., self‐renewing and multipotency); 2) lineage differentiation (i.e., ability to develop mature cells in specific “maturation” times, often measured as the delay between the introduction of a stimulus, like chemotherapy, and results); and 3) negative feedback loops in response to stimuli (i.e., key regulators of the process). However, many models focus only on a specific type of myelosuppression (e.g., drug‐induced neutropenia), and so they do not consider multipotency and multilineages.…”

“…Mathematical modeling, coupled with experimental observations, is an effective tool to close this gap, enabling the extrapolation of underlying cell behaviors and dynamics from experimental data. For example, Busch et al .…”

Kinetic models of hematopoietic differentiation

“…We confine ourselves in here to the latter. Good reviews exist covering population models in this context (see e.g., MacLean, Celso, & Stumpf, ). However, initiatives to fuse the two levels will be touched upon below.…”