Presentation Information
[C06-03]Mathematical modeling of hematopoiesis by age-specific and lineage-restricted hematopoietic stem cells
*Shoya iwanami1 (1. Nagoya University (Japan))
Keywords:
Hematopoietic stem cell,Aging,Cell differentiation
Hematopoietic stem cells (HSCs) are a population of cells at the apex of blood cell differentiation, maintaining the hematopoietic system through self-renewal and multipotency. In recent years, the diversity of HSCs has been observed through gene expression analysis using single-cell RNA sequencing and clonal tracking with genetic barcoding. Single-cell transplantation experiments have suggested the existence of cells—termed latent-HSCs—that, despite showing lineage-restricted differentiation initially, possess long-term reconstitution potential and latent multipotency, particularly in the context of aging, as revealed through large-scale evaluation. Furthermore, a non-hierarchical relationship has been observed between HSCs with long-term platelet-producing capacity and those with multipotent differentiation potential. It is now believed that multipotency is not an essential criterion for HSCs; rather, cell populations with long-term productivity maintain hematopoiesis as stem cell populations.
The key question here lies in the existence, differentiation mechanisms, and role in hematopoiesis of lineage-restricted hematopoietic cells. Focusing on the differentiation and hematopoietic contribution of latent-HSCs observed in single-cell transplantation experiments, we constructed a differentiation model of HSCs with distinct properties. To reproduce the phenomenon in which differentiation is initially restricted to specific lineages in primary transplantation but becomes multipotent in secondary transplantation, we conducted probabilistic simulations of cell differentiation under transplantation conditions. Special attention was given to the existence of lineage-restricted stem cells, plasticity among stem cells, and the effect of rarity induced by transplantation, analyzing their relationship with the emergence of latent-HSCs as phenotypes post-transplantation. Analyzing the differentiation dynamics of HSCs using mathematical models is expected to provide a unified understanding of the diverse HSC characteristics observed from various perspectives.
The key question here lies in the existence, differentiation mechanisms, and role in hematopoiesis of lineage-restricted hematopoietic cells. Focusing on the differentiation and hematopoietic contribution of latent-HSCs observed in single-cell transplantation experiments, we constructed a differentiation model of HSCs with distinct properties. To reproduce the phenomenon in which differentiation is initially restricted to specific lineages in primary transplantation but becomes multipotent in secondary transplantation, we conducted probabilistic simulations of cell differentiation under transplantation conditions. Special attention was given to the existence of lineage-restricted stem cells, plasticity among stem cells, and the effect of rarity induced by transplantation, analyzing their relationship with the emergence of latent-HSCs as phenotypes post-transplantation. Analyzing the differentiation dynamics of HSCs using mathematical models is expected to provide a unified understanding of the diverse HSC characteristics observed from various perspectives.