Adaptive dynamics of hematopoietic stem cells and their supporting stroma: a model and mathematical analysis

Thanh Nam Nguyen1,2, Jean Clairambault1, Thierry Jaffredo3

  • 1Sorbonne Université, Université Paris-Diderot, CNRS, INRIA, Laboratoire Jacques-Louis Lions, F-75005 Paris, France.

We propose a mathematical model to describe the evolution of hematopoietic stem cells (HSCs) and stromal cells in considering the bi-directional interaction between them. Cancerous cells are also taken into account in our model. HSCs are structured by a continuous phenotype characterising the population heterogeneity in a way relevant to the question at stake while stromal cells are structured by another continuous phenotype representing their capacity of support to HSCs. We then analyse the model in the framework of adaptive dynamics. More precisely, we study single Dirac mass steady states, their linear stability and we investigate the role of parameters in the model on the nature of the evolutionary stable distributions (ESDs) such as monomorphism, dimorphism and the uniqueness properties. We also study the dominant phenotypes by an asymptotic approach and we obtain the equation for dominant phenotypes. Numerical simulations are employed to illustrate our analytical results. In particular, we represent the case of the invasion of malignant cells as well as the case of co-existence of cancerous cells and healthy HSCs.

Related Concept Videos

Isolation Method for Long-Term and Short-Term Hematopoietic Stem Cells06:41

Isolation Method for Long-Term and Short-Term Hematopoietic Stem Cells

We present a step-by-step protocol for the isolation of long-term hematopoietic stem cells (LT-HSCs) and short-term HSCs (ST-HSCs) using the Hoxb5 reporter...
2.5K
Derivation of Hematopoietic Stem Cells from Murine Embryonic Stem Cells22:06

Derivation of Hematopoietic Stem Cells from Murine Embryonic Stem Cells

This protocol details the derivation of transplantable hematopoietic stem cells from mouse embryonic stem cells (ESC) and their subsequent injection into lethally irradiated recipient mice. Briefly, ESC are differentiated as embryoid bodies, which are then infected with retroviral HoxB4 and co-cultured with OP9 stromal cells and hematopoietic...
14.0K
Isolation and Analysis of Hematopoietic Stem Cells from the Placenta14:42

Isolation and Analysis of Hematopoietic Stem Cells from the Placenta

We have identified the placenta as a major hematopoietic organ during development. We found that hematopoietic stem cells (HSCs) are both generated and expanded in the placenta in unique microenvironmental niches. Here, we describe experimental techniques required for isolation and visualization of HSCs in the mouse...
21.0K
Analysis of Hematopoietic Stem Progenitor Cell Metabolism12:20

Analysis of Hematopoietic Stem Progenitor Cell Metabolism

Hematopoietic stem progenitor cells (HSPCs) transition from a quiescent state to a differentiation state due to their metabolic plasticity during blood formation. Here, we present an optimized method for measuring mitochondrial respiration and glycolysis of...
7.3K
Preparation and Gene Modification of Nonhuman Primate Hematopoietic Stem and Progenitor Cells11:16

Preparation and Gene Modification of Nonhuman Primate Hematopoietic Stem and Progenitor Cells

The goal of this protocol is to isolate nonhuman primate CD34+ cells from primed bone marrow, to gene-modify these cells with lentiviral vectors, and to prepare a product for infusion into the autologous host. The total protocol length is approximately 48...
8.0K
Isolation and Transplantation of Hematopoietic Stem Cells (HSCs)20:38

Isolation and Transplantation of Hematopoietic Stem Cells (HSCs)

24.2K