The Reticulocyte

Samuel Rapoport

• Publisher: CRC Press
• Year: 2020
• ISBN:
  9781000083347
• Edition: 1
• Topic: Biological Sciences
• Subtopic: Cell Biology
• Index: Biological Sciences

First Published in 1986, this book offers a full, comprehensive guide to immature red blood cells. Carefully compiled and filled with a vast repertoire of notes, diagrams, and references this book serves as a useful reference for Students of Medicine, and other practitioners in their respective fields.

Biology of Erythroid Cells and Reticulocytes

Chapter 1

Survey of Early Erythroid Differentiation

I. Introduction

Present-day research is centered on elucidation of the intrinsic and extrinsic factors instrumental in the initiation and realization of the differentiation program.

Erythroid differentiation may well be the best model for the study of general problems of differentiation, even though it has undoubtedly specific features. Among the advantages of the erythroid model are (1) the cell specialization with the predominance of one terminal product, hemoglobin, which comprises about 95% of the final complement of proteins; (2) the existence of a series of stages which can be recognized by morphological, biochemical, and immunological methods; (3) the possibility to obtain considerable numbers of differentiating cells from discrete sites; (4) the development of cell lines in which erythroid maturation has been arrested. These cells are inducible to further differentiation by a variety of chemical agents; (5) the fact that hemoglobin is the product of more than one gene and requires for its synthesis coordinate expression of several genes; also in many species there occur during ontogeny shifts in the type of populations of red cells and of hemoglobins (switching); (6) the regulation of red cell production by a defined hormonal system.

Among the problems that are being approached are (1) the nature of commitment to a particular cell type; (2) the coordination of multigene families in ontogeny and differentiation; (3) the structural arrangement of simultaneously or sequentially expressed genes; (4) the nature of gene activation and suppression; (5) the relationship between cell division, DNA synthesis, and the transitions between differentiation stages; (6) synthesis, processing, unmasking, and stability of RNA during differentiation; (7) the relation between differentiation and malignant transformation.

Several critical steps may be discerned in the differentiation programs of erythroid cells. They include: (1) proliferation of the pluripotent hematopoietic stem cells; (2) commitment of the stem cells to erythropoiesis; (3) proliferation of the committed erythroid precursors, a phase which includes several sequential stages; and (4) realization of the program characteristic of terminal differentiation.

II. Stem Cells and Other Progenitors

It is well known that most types of blood cells, including erythrocytes, thrombocytes, granulocytes, megakaryocytes, and monocytes, are derived from one common stem cell compartment by multistage processes. It is customary to divide the progenitor cells into several subcompartments. The most primitive pluripotential hemopoietic stem cells, which are capable both of cell replication and of generating the subsequent stages, i.e., cells committed to differentiation, are the least well defined. The compartment of committed stem cells has become accessible by the development of in vitro and in vivo clonal assays for the different cell types (see Ogawa et al¹). In this manner cell lineages were found with more than one potential both from human and mouse sources. Of particular interest as candidates for the pluripotential stem cells were the CFU-GEMM (granulocytes, erythrocytes, macrophages, megakaryocytes).^2-4 Some observations suggest that even CFU-S and CFU-GEMM cells are still relatively mature pluripotent progenitors and that there exist truly primitive stem cells which are characterized by their extensive repopulating ability of bone marrow.¹

Only recently success was reported in the identification of a unique type of hemopoietic colony of mice which consisted only of undifferentiated blast cells which may be the long sought-after primitive stem cell.⁵ These cells show no sign of terminal differentiation and appear to be the precursors of the CFU-GEMM cells. The presumptive true stem cells have both the capacity of self-renewal and of differentiation. Clonal analysis indicates that the decision of a given cell either to enter the pathway of differentiation or of self-renewal may be a random event.⁶ A schematic survey of a possible sequence of the differentiation of hemopoietic stem cells based on culture assays is presented in Figure 1.

FIGURE 1. Schematic survey of differentiation sequence of erythroid cells. S-cells, uncommitted, undifferentiated stem cells; GEMM, colony-forming unit, granulocyte, erythrocyte, macrophage megakaryocyte; MEBT, megakaryocyte, erythrocyte, B- and T-lymphocyte; GEM, granulocyte, erythrocyte, megakaryocyte; EM, erythrocyte, megakaryocyte; GE, granulocyte, erythrocyte; BFU-E, burst-forming unit, erythrocyte; CFU-E, colony-forming unit, erythrocyte; EPO, erythropoietin.

The various progenitors depend on a variety of so-called colony-stimulating factors and modulators, the discussion of which is beyond the scope of this survey. The most primitive monopotent class of erythroid progenitor cells are called BFU-E (burst forming unit erythroid) and apparent...

Table of contents

• Cover
• Title Page
• Copyright Page
• Preface
• The Author
• Introductory Remark: Differentiation and Maturation
• Table of Contents
• BIOLOGY OF ERYTHROID CELLS AND RETICULOCYTES
• METABOLISM OF RETICULOCYTES
• MECHANISMS OF MATURATION OF THE RETICULOCYTE
• Index