Cell Lineage Choice During Haematopoiesis: A Commemorative Issue in Honor of Professor Antonius Rolink

ca. 200 words; this text will present the book in all promotional forms (e.g. flyers). Please describe the book in straightforward and consumer-friendly terms. This special issue of the International Journal of Molecular Sciences contains a collection of articles by colleagues of Antonius (Ton) Gerardus Rolink (19/04/1953-06/08/2017) and honors Ton’s life and profound knowledge of and huge contribution to science. Ton participated in an FP7 Marie Curie Initial Training Network called DECIDE, and partners have submitted articles for this Special Issue. Scientists outside this network have also submitted articles. The articles examine various aspects of how the hematopoietic stem-cell gives rise to the different types of blood and immune cells. These include decision-making by the hematopoietic stem cell and the importance of controlling events within cells and the niches the cell resides in. New insights into these processes at the basic scientific level have given rise to an emerging new model for the development of blood cells. In turn, changes to our understanding of this process have led to new and exciting propositions regarding what goes wrong during the early stages of the development of leukemia

The changing face of haematopoiesis: A spectrum of options is available to stem cells

For more than 30 years, the scheme whereby bone marrow hematopoietic stem cells give rise to the many different types of blood and immune cells has been represented as a lineage tree diagram. In this model, hematopoietic stem cells follow a preferred route to each of the end‐cell types and gradually restrict their other lineage options via a series of intermediate oligo‐potent progenitors. Recent findings of lineage biases or affiliations within hematopoietic stem and progenitor cells that are either pluripotent or uni‐potent show that a continuum of fate options is open to hematopoietic stem cells. These results support the view that in order to close down developmental options, hematopoietic stem cells can make an immediate lineage choice rather than become gradually committed as they progress step‐wise through a series of intermediate progenitors. In this scenario, there is inherent versatility in that developing cells are still able to move sideways to adopt an alternative lineage fate. Here, we examine the information that is leading toward this very different viewpoint of blood cell development

Cell lineage choice during hematopoiesis:in honor of Professor Antonius Rolink

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Effects of unidirectional flow shear stresses on the formation, fractal microstructure and rigidity of incipient whole blood clots and fibrin gels

Incipient clot formation in whole blood and fibrin gels was studied by the rheometric techniques of controlled stress parallel superposition (CSPS) and small amplitude oscillatory shear (SAOS). The effects of unidirectional shear stress on incipient clot microstructure, formation kinetics and elasticity are reported in terms of the fractal dimension (df) of the fibrin network, the gel network formation time (TGP) and the shear elastic modulus, respectively. The results of this first haemorheological application of CSPS reveal the marked sensitivity of incipient clot microstructure to physiologically relevant levels of shear stress, these being an order of magnitude lower than have previously been studied by SAOS. CSPS tests revealed that exposure of forming clots to increasing levels of shear stress produces a corresponding elevation in df, consistent with the formation of tighter, more compact clot microstructures under unidirectional flow. A corresponding increase in shear elasticity was recorded. The scaling relationship established between shear elasticity and df for fibrin clots and whole blood confirms the fibrin network as the dominant microstructural component of the incipient clot in terms of its response to imposed stress. Supplementary studies of fibrin clot formation by rheometry and microscopy revealed the substantial additional network mass required to increase df and provide evidence to support the hypothesis that microstructural changes in blood clotted under unidirectional shear may be attributed to flow enhanced thrombin generation and activation. CSPS also identified a threshold value of unidirectional shear stress above which no incipient clot formation could be detected. CSPS was shown to be a valuable haemorheological tool for the study of the effects of physiological and pathological levels of shear on clot properties

Validation of Optimal Fourier Rheometry for rapidly gelling materials and its application in the study of collagen gelation

Rheological Gel Point measurements may incur errors in the case of rapid gelling systemsdue to the limitations of multiple frequency oscillatory shear techniques such as frequency sweeps and Fourier Transform Mechanical Spectroscopy, FTMS. These limitations are associated with sample mutation and data interpolation. In the present paper we consider how an alternative rapid characterisation technique known as Optimal Fourier Rheometry, OFR, can be used to study a rapidly gelling material, namely collagen at near physiological temperatures. The OFR technique is validated using a model reference gelling system whose GP characteristics have been widely reported. An analysis of the susceptibility of OFR measurements to rheometrical artefacts is made prior to its use in study of rapid gelling collagen gels formed over a range of physiologically relevant collagen concentrations. The results of this OFR are the first measurements of the stress relaxation characteristics of collagen gels in a single rheological experiment

Assessment of the stress relaxation characteristics of critical gels formed under unidirectional shear flow by controlled stress parallel superposition rheometry

Processes involving a unidirectional shear flow component are widespread in industrial manufacturing techniques such as printing and coating, or in physiological events such as blood coagulation. Standard rheometric techniques are usually employed under quiescent conditions and as such are inappropriate for the study of microstructural modification induced by the presence of a unidirectional shear flow. We demonstrate how controlled stress parallel superposition (CSPS) may be exploited to enable accurate detection of the Gel Point and analysis of Gel Point parameters for systems undergoing a viscoelastic liquid (VEL) to viscoelastic solid (VES) transition in the presence of a unidirectional flow field. Specifically, we note that certain features of the CSPS experiment, when performed near the Gel Point, may obviate previously reported concerns regarding the experiment. A biopolymer system (gelatin) which forms gels by thermoreversible gelation is employed as a model gelling material to confirm the ability of CSPS to characterise the stress relaxation characteristics of critical-gels in the presence of a) progressively decreasing and b) progressively increasing unidirectional strain rate and oscillatory strain amplitude. Additional validation of CSPS results is reported for a silicone dielectric gel used in the industrial production of printed electronic products. Finally, CSPS is used to investigate microstructural modification of fibrin-thrombin gels as a consequence of clot formation under a unidirectional shear stress. The results confirm the validity of the CSPS technique in gelation studies and the technique is used, for the first time, to directly record the thermally induced VES to VEL transition in aqueous gelatin systems

The making of hematopoiesis::Developmental ancestry and environmental nurture

Evidence from studies of the behaviour of stem and progenitor cells and of the influence of cytokines on their fate determination, has recently led to a revised view of the process by which hematopoietic stem cells and their progeny give rise to the many different types of blood and immune cells. The new scenario abandons the classical view of a rigidly demarcated lineage tree and replaces it with a much more continuum-like view of the spectrum of fate options open to hematopoietic stem cells and their progeny. This is in contrast to previous lineage diagrams, which envisaged stem cells progressing stepwise through a series of fairly-precisely described intermediate progenitors in order to close down alternative developmental options. Instead, stem and progenitor cells retain some capacity to step sideways and adopt alternative, closely related, fates, even after they have “made a lineage choice.” The stem and progenitor cells are more inherently versatile than previously thought and perhaps sensitive to lineage guidance by environmental cues. Here we examine the evidence that supports these views and reconsider the meaning of cell lineages in the context of a continuum model of stem cell fate determination and environmental modulation

A new biomarker quantifies differences in clot microstructure in patients with venous thromboembolism

This study compared patients with venous thromboembolism (VTE) to non‐VTE patients using a biomarker of clot microstructure (df) and clot formation time (TGP). df was the only marker that identified a significant difference (P < 0·001) between the VTE (n = 60) and non‐VTE cohorts (n = 69). The ‘abnormal’ clot microstructures in the VTE patients suggests either inadequate response to anticoagulant therapy or the presence of a procoagulant state not detected by other markers of coagulation (i.e., International Normalized Ratio). Furthermore, elevated values of df in first time VTE patients who later develop a secondary event indicates that df may identify those at risk of recurrence