The Experts below are selected from a list of 237 Experts worldwide ranked by ideXlab platform

Robert F. Paulson - One of the best experts on this subject based on the ideXlab platform.

  • Stress Erythropoiesis: definitions and models for its study.
    Experimental Hematology, 2020
    Co-Authors: Robert F. Paulson, Sneha Hariharan, Jane A. Little
    Abstract:

    Steady state Erythropoiesis generates new erythrocytes at a constant rate, and it has an enormous productive capacity. This production is balanced by the removal of senescent erythrocytes by macrophages in the spleen and liver. Erythroid homeostasis is highly regulated to maintain sufficient erythrocytes for efficient oxygen delivery to the tissues, while avoiding viscosity problems associated with over-production. However, there are times when this constant production of erythrocytes is inhibited or is inadequate, at these times, erythroid output is increased to compensate for the loss of production. In some cases, increased steady state Erythropoiesis can offset the loss of erythrocytes but, in response to inflammation caused by infection or tissue damage, steady state Erythropoiesis is inhibited. To maintain homeostasis under these conditions, an alternative stress Erythropoiesis pathway is activated. Emerging data suggest that the BMP4 dependent stress Erythropoiesis pathway is integrated into the inflammatory response and generates a bolus of new erythrocytes that maintains homeostasis until steady state Erythropoiesis can resume. In this perspective, we define the mechanisms that generate new erythrocytes when steady state Erythropoiesis is impaired and discuss experimental models to study human stress Erythropoiesis.

  • Stress Erythropoiesis is a Key Inflammatory Response.
    Cells, 2020
    Co-Authors: Robert F. Paulson, Baiye Ruan, Yuanting Chen
    Abstract:

    Bone marrow medullary Erythropoiesis is primarily homeostatic. It produces new erythrocytes at a constant rate, which is balanced by the turnover of senescent erythrocytes by macrophages in the spleen. Despite the enormous capacity of the bone marrow to produce erythrocytes, there are times when it is unable to keep pace with erythroid demand. At these times stress Erythropoiesis predominates. Stress Erythropoiesis generates a large bolus of new erythrocytes to maintain homeostasis until steady state Erythropoiesis can resume. In this review, we outline the mechanistic differences between stress Erythropoiesis and steady state Erythropoiesis and show that their responses to inflammation are complementary. We propose a new hypothesis that stress Erythropoiesis is induced by inflammation and plays a key role in maintaining erythroid homeostasis during inflammatory responses.

  • Stress Erythropoiesis Model Systems.
    Methods of Molecular Biology, 2017
    Co-Authors: Laura Bennett, Chang Liao, Robert F. Paulson
    Abstract:

    Bone marrow steady-state Erythropoiesis maintains erythroid homeostasis throughout life. This process constantly generates new erythrocytes to replace the senescent erythrocytes that are removed by macrophages in the spleen. In contrast, anemic or hypoxic stress induces a physiological response designed to increase oxygen delivery to the tissues. Stress Erythropoiesis is a key component of this response. It is best understood in mice where it is extramedullary occurring in the adult spleen and liver and in the fetal liver during development. Stress Erythropoiesis utilizes progenitor cells and signals that are distinct from bone marrow steady-state Erythropoiesis. Because of that observation many genes may play a role in stress Erythropoiesis despite having no effect on steady-state Erythropoiesis. In this chapter, we will discuss in vivo and in vitro techniques to study stress Erythropoiesis in mice and how the in vitro culture system can be extended to study human stress Erythropoiesis.

  • Targeting a new regulator of Erythropoiesis to alleviate anemia.
    Nature Medicine, 2014
    Co-Authors: Robert F. Paulson
    Abstract:

    Anemia is a debilitating condition that can be complicated by ineffective Erythropoiesis. Two new studies identify GDF11 as a regulator of Erythropoiesis and show that its inhibition in mouse models of anemia with ineffective Erythropoiesis restores normal erythropoietic differentiation and alleviates anemia (pages 398–407 and 408–414).

  • stress Erythropoiesis new signals and new stress progenitor cells
    Current Opinion in Hematology, 2011
    Co-Authors: Robert F. Paulson, Daichen Wu
    Abstract:

    Purpose of reviewAcute anemic stress induces a physiological response that includes the rapid development of new erythrocytes. This process is referred to as stress Erythropoiesis, which is distinct from steady state Erythropoiesis. Much of what we know about stress Erythropoiesis comes from the ana

Daichen Wu - One of the best experts on this subject based on the ideXlab platform.

Vijay G Sankaran - One of the best experts on this subject based on the ideXlab platform.

  • Erythropoiesis
    Oxford Textbook of Medicine, 2020
    Co-Authors: Vijay G Sankaran
    Abstract:

    Erythropoiesis is a highly regulated, multistep process in which stem cells, after a series of amplification divisions, generate multipotential progenitor cells, then oligo- and finally unilineage erythroid progenitors, and then morphologically recognizable erythroid precursors and mature red cells. The ontogeny of Erythropoiesis involves a series of well-coordinated events during embryonic and early fetal life. In the fetus, the main site of Erythropoiesis is the liver, which initially produces mainly fetal haemoglobin (HbF, α‎2γ‎2) and a small component (10–15%) of adult haemoglobin (HbA, α‎2β‎2), with the fraction of HbA rising to about 50% at birth. After birth, the site of erythroid cell production maintained throughout life is the bone marrow, with the final adult erythroid pattern (adult Hb with <1% fetal Hb) being reached a few months after birth. Regulation of Erythropoiesis—the main regulator is erythropoietin, a sialoglycoprotein that is produced by interstitial cells in the kidney in response to tissue hypoxia and exerts its effect by binding to a specific receptor on erythroid burst-forming units, erythroid colony-forming units, and proerythroblasts. Abnormal erythropoietin production—anaemia can be caused by acquired or congenital deficiency in erythropoietin production, most commonly in chronic kidney disease. Impaired tissue oxygen delivery is a common cause of erythropoietin-driven secondary erythrocytosis. Some kidney cancers increase erythropoietin production and hence cause secondary erythrocytosis. Other causes of abnormal erythroid production include (1) acquired and congenital defects in erythropoietin signalling; (2) acquired and congenital defects in the transcription factors GATA1 or EKLF; (3) acquired or congenital abnormalities in ribosome synthesis or splicing factors; and (4) factors that lead to premature red cell destruction.

  • advances in understanding Erythropoiesis evolving perspectives
    British Journal of Haematology, 2016
    Co-Authors: Satish K Nandakumar, Jacob C Ulirsch, Vijay G Sankaran
    Abstract:

    Summary Red blood cells (RBCs) are generated from haematopoietic stem and progenitor cells (HSPCs) through the step-wise process of differentiation known as Erythropoiesis. In this review, we discuss our current understanding of Erythropoiesis and highlight recent advances in this field. During embryonic development, Erythropoiesis occurs in three distinct waves comprising first, the yolk sac-derived primitive RBCs, followed sequentially by the erythro-myeloid progenitor (EMP) and HSPC-derived definitive RBCs. Recent work has highlighted the complexity and variability that may exist in the hierarchical arrangement of progenitors responsible for Erythropoiesis. Using recently defined cell surface markers, it is now possible to enrich for erythroid progenitors and precursors to a much greater extent than has been possible before. While a great deal of knowledge has been gained on Erythropoiesis from model organisms, our understanding of this process is currently being refined through human genetic studies. Genes mutated in erythroid disorders can now be identified more rapidly by the use of next-generation sequencing techniques. Genome-wide association studies on erythroid traits in healthy populations have also revealed new modulators of Erythropoiesis. All of these recent developments have significant promise not only for increasing our understanding of Erythropoiesis, but also for improving our ability to intervene when RBC production is perturbed in disease.

  • rb intrinsically promotes Erythropoiesis by coupling cell cycle exit with mitochondrial biogenesis
    Genes & Development, 2008
    Co-Authors: Vijay G Sankaran, Stuart H Orkin, Carl R Walkley
    Abstract:

    Regulation of the cell cycle is intimately linked to erythroid differentiation, yet how these processes are coupled is not well understood. To gain insight into this coordinate regulation, we examined the role that the retinoblastoma protein (Rb), a central regulator of the cell cycle, plays in Erythropoiesis. We found that Rb serves a cell-intrinsic role and its absence causes ineffective Erythropoiesis, with a differentiation block at the transition from early to late erythroblasts. Unexpectedly, in addition to a failure to properly exit the cell cycle, mitochondrial biogenesis fails to be up-regulated concomitantly, contributing to this differentiation block. The link between Erythropoiesis and mitochondrial function was validated by inhibition of mitochondrial biogenesis. Erythropoiesis in the absence of Rb resembles the human myelodysplastic syndromes, where defects in cell cycle regulation and mitochondrial function frequently occur. Our work demonstrates how these seemingly disparate pathways play a role in coordinately regulating cellular differentiation.

Lawrence T Goodnough - One of the best experts on this subject based on the ideXlab platform.

  • iron deficiency syndromes and iron restricted Erythropoiesis cme
    Transfusion, 2012
    Co-Authors: Lawrence T Goodnough
    Abstract:

    The relationships between erythropoietin (EPO), iron, and Erythropoiesis and the presence of iron-restricted Erythropoiesis have important implications in anemia management. Iron-restricted Erythropoiesis occurs in the presence of one or more iron deficiency syndromes: absolute iron deficiency, functional iron deficiency, and/or iron sequestration. Absolute iron deficiency is a common nutritional deficiency in women's health, pediatrics, and the elderly and is therefore an important public health problem. Functional iron deficiency occurs in patients with significant EPO-mediated Erythropoiesis or therapy with Erythropoiesis-stimulating agents, even when storage iron is present. Iron sequestration mediated by hepcidin is an underappreciated but common cause of iron-restricted Erythropoiesis in patients with chronic inflammatory disease. The challenge for treating and laboratory-based physicians is to understand the contributory role(s) of each of these syndromes, so that the potential value of emerging and innovative pharmacologic strategies can be considered as options in patient blood management.

  • detection evaluation and management of iron restricted Erythropoiesis
    Blood, 2010
    Co-Authors: Lawrence T Goodnough, Elizabeta Nemeth, Tomas Ganz
    Abstract:

    Progress in our understanding of iron-restricted Erythropoiesis has been made possible by important advances in defining the molecular mechanisms of iron homeostasis. The detection and diagnostic classification of iron-restricted Erythropoiesis can be a challenging process for the clinician. Newer assays for markers of inflammation may allow more targeted management of the anemia in these conditions. The availability of new intravenous iron preparations provides new options for the treatment of iron-restricted Erythropoiesis. This review summarizes recent advances regarding the detection, evaluation, and management of iron-restricted Erythropoiesis.

  • The Relevance of Iron in Erythropoietin-Stimulated Erythropoiesis
    Seminars in Hematology, 2006
    Co-Authors: Lawrence T Goodnough
    Abstract:

    Several clinical models have generated insight into the relationship between erythropoietin (EPO), iron, and Erythropoiesis. Patients with chronic hemolytic anemias or hemochromatosis can increase Erythropoiesis six- to eightfold over basal rates, whereas patients with blood loss, such as those donating autologous blood, can increase Erythropoiesis only two- to fourfold over basal levels, even with pharmacologic doses of recombinant human EPO. A substantial limitation to the dose/response relationship between EPO therapy and the erythropoietic response is iron-restricted Erythropoiesis, even in the presence of storage iron. Novel approaches to iron supplementation therapy when erythropoietic agents are used are indicated.

Elizabeta Nemeth - One of the best experts on this subject based on the ideXlab platform.