Multistage feedback driven compartmental dynamics of hematopoiesis

Human hematopoiesis is surprisingly resilient to disruptions, providing suitable responses to severe bleeding, long lasting immune activation, and even bone marrow transplants. Still, many blood disorders exist which push the system past its natural plasticity, resulting in abnormalities in the circulating blood. While proper treatment of such diseases can benefit from understanding the underlying cell dynamics, these are non-trivial to predict due to the hematopoietic system’s hierarchical nature and complex feedback networks. To characterize the dynamics following different types of perturbations we investigate a model representing hematopoiesis as a sequence of compartments covering all maturation stages – from stem to mature cells – where feedback regulates cell production to ongoing necessities. We find that a stable response to perturbations requires the simultaneous adaptation of cell differentiation and self-renewal rates, and show that under conditions of continuous disruption – as found in chronic hemolytic states – compartment cell numbers evolve to novel stable states.

New insight derived from a two-compartment cell: electrochemical behavior of FeF3 positive electrode

A designed two-compartment cell revealed the degradation mechanism and an essentially effective additive for the FeF3 composite electrode.

The Myeloid Cell Compartment—Cell by Cell

Myeloid cells are a major cellular compartment of the immune system comprising monocytes, dendritic cells, tissue macrophages, and granulocytes. Models of cellular ontogeny, activation, differentiation, and tissue-specific functions of myeloid cells have been revisited during the last years with surprising results; for example, most tissue macrophages are yolk sac derived, monocytes and macrophages follow a multidimensional model of activation, and tissue signals have a significant impact on the functionality of all these cells. While these exciting results have brought these cells back to center stage, their enormous plasticity and heterogeneity, during both homeostasis and disease, are far from understood. At the same time, the ongoing revolution in single-cell genomics, with single-cell RNA sequencing (scRNA-seq) leading the way, promises to change this. Prevailing models of hematopoiesis with distinct intermediates are challenged by scRNA-seq data suggesting more continuous developmental trajectories in the myeloid cell compartment. Cell subset structures previously defined by protein marker expression need to be revised based on unbiased analyses of scRNA-seq data. Particularly in inflammatory conditions, myeloid cells exhibit substantially vaster heterogeneity than previously anticipated, and work performed within large international projects, such as the Human Cell Atlas, has already revealed novel tissue macrophage subsets. Based on these exciting developments, we propose the next steps to a full understanding of the myeloid cell compartment in health and diseases.