- Email: [email protected]
Handbook of the hemopoietic microenvironment
Cell, Vol. 61, 557-560,
May 16, 1990, Copyright
0 1990 by Cell Press
Book Reviews
Fertile Soil for Hemopoiesis Handbook of the Hemopoietic Microenvironment. Edited by M. Tavassoli. Clifton, New Jersey: Humana Press. (1989). 453 pp. $79.50.
The preface to this volume on the hemopoietic microenvironment contains a quotation made in 1918 by the Russian embryologist Vera Danchakoff that likens the bone marrow to a fertile soil in which the seed, in this case the hemopoietic stem cell, can develop. The aim of this volume is to describe what is known about the structure and function of the bone marrow environment. This is a timely undertaking because this specific area is rapidly evolving owing to the application of modern approaches in cell and molecular biology to its study. The term hemopoietic microenvironment is a catchall phrase that encompasses the cells, collectively referred to as stromal cells, and cell products, such as cytokines and extracellular matrix components, that form the supporting milieu for blood cell development. These microenvironmental elements are reviewed in 12 chapters, each written by a different author(s). The introductory chapter by Trentin provides a historical perspective of the field and an interesting discussion aimed at reconciling the long-debated issue of whether microenvironmental influences on stem cells are inductive or permissive. The remaining chapters address specific topics that include microenvironmental components, stromal cells in culture, interactions between stromal and hemopoietic cells, in vivo and in vitro methods to study the microenvironment, the extracellular matrix, and clinical applications. An excellent contribution for those just entering the field is the chapter by Lichtman and colleagues on bone marrow structure. This provides an overview of the medullary circulation, a summary of the different types of morphologically recognizable stromal cells and their spatial organization, and their relationship to hemopoietic cells. Additional portions of the book, such as the chapter by Tavassoli on adipocytes, deal in more detail with specific stromal cell types. If the definition of the hemopoietic microenvironment is taken to include any cell population that can influence hemopoiesis, then selected hemopoietic cells such as macrophages, natural killer (NK) cells, and T lymphocytes may also be considered to be constitutive elements. Reference to the role of macrophages is made throughout the book, and the effects of T cells and NK cells on human hemopoiesis are discussed in a chapter by Ascensao and Zanjani. However, the principal focus of the volume is on the sessile, connective tissue stromal cells. A major aim of workers in this field is to define the mechanisms by which stromal cells regulate hemopoiesis. The development of various long-term bone marrow culture systems can arbitrarily be chosen as marking the begin-
ning of the current era of research in this area. These cultures have in common the formation of a marrow-adherent layer in culture that apparently duplicates the environment present in the medullary cavity. Specific conditions have been developed by Dexter and colleagues and by Whitlock and Witte that permit the long-term production of myeloid or B lymphoid cells, respectively. The chapter by Quesenberry reviews these systems and how they have been used to study hemopoiesis in mice, humans, and other species, and a contribution by Shaklai compares the morphology of stromal cells grown in vitro to those observed in vivo. It is important to note that considerable efforts to dissect the hemopoietic microenvironment were made long before the advent of long-term cultures, and readers of the book will gain an appreciation for some of these experimental approaches, which include transplantation of cultured stromal cells or fresh marrow plugs to ectopic sites in vivo, in vivo microscopy, and the growth of hemopoietic cells on artificial membranes. Many laboratories have cloned stromal cells from the marrow or the adherent layers of long-term cultures; these have been of value in studies of particular environmental components and how these cells regulate blood cell production. The various stromal cell lines have been extensively characterized by phenotypic, morphologic, and biochemical means, as well as in functional assays in which their hemopoietic support capacity has been measured. The chapter by Quesenberry and another by Zipori provide an extensive review of some of the stromal cell lines, their characteristics, and how they have been used to study myelopoiesis and lymphopoiesis. Another topic of current interest is the study of the extracellular matrix (ECM). The role of the ECM in influencing cell migration, proliferation, and other developmental processes is now widely appreciated. The two informative chapters on the collagenous and noncollagenous ECM provide a background about the biochemistry of various matrix components, their distribution in fresh and cultured marrow, and how they may influence normal and dysregulated hemopoiesis. Because analysis of the hemopoietic system attracts investigators from multiple disciplines and new developments are rapid, it is difficult for a single review article, or even a book devoted to the topic, to address all relevant points or be completely up-to-date. Consequently, there are specific topics not discussed in detail in this volume. For example, stromal cells are known to be the source of multiple growth and differentiation factors. While many of these, particularly the colony-stimulating factors, are reviewed in the book, there has been progress in cloning additional stromal cell genes that encode novel hemopoietic factors, such as interleukin-7, a molecule that stimulates the proliferation of B cell progenitors. Another topic not addressed in detail is cytokine networks. As a result of their expression of various cytokine receptors, stromal cells are sensitive to conditions in their external milieu, and this can affect the types and level of factors secreted
Cell 558
by them. Additional rapidly evolving topics are the role of the ECM in binding hemopoietic cells of particular lineages and maturational states, and the binding of hemopoietic growth factors to ECM components. Complete, up-to-date information regarding the hemopoietic microenvironment will require the reading of this book in conjunction with more recent reviews and primary literature. However, this should not detract from strengths that include coverage of a wide range of topics, the presentation of a historical perspective of the field, and an easy-to-read format. In addition, the extensive reference lists at the end of most chapters provide a valuable bibliography. Kenneth Dorshkind Division of Biomedical Sciences University of California Riverside, California 92521
Protein Structural Clairvoyance Prediction of Protein Edited by New York:
of Protein Structure and Principles Conformation. G. D. Fasman. Plenum Press. (1989). 798 pp. $95.00.
With increasing frequency I get telephone calls or spontaneous visits from PCR-clone-sequence-site-specificmutagenize types who show me the predicted amino acid sequence from an open reading frame that has been entered into a packaged secondary-structure prediction algorithm. The question is, “Can you recommend an X-ray crystallographer or NMR spectroscopist to confirm my discovery that there is a zinc finger stuck in my leucine zipper?“Thus, this is a timely book which is required reading for all of us who deal with phenomena resulting from the interaction of biological macromolecules. Furthermore, as a public service a number of algorithms were collected and deposited at several national resources (appendix 2, p. 305). I will start with the bottom line-this will be a required text in our graduate-level course in biophysical chemistry. This does not imply that this is an excellent, well-written, or up-to-date book. What is important is that it addresses all the issues implied in the title. Students learn more from texts that are imperfect; instructors look better when the textbook deficiencies are obvious and easy to remedy. The subject builds on our training that the primary sequence of proteins determines the secondary structure, which in turn leads to tertiary structure and quaternary structure. Fasman has gathered most of the active workers in the field of protein structures, working on topics ranging from molecular dynamics (McCammon and Hagler; chapters 4 and 7) to protein crystallography (Richardsons, Deisenhofer, Stubbs; chapters l-3). There are chapters describing the prediction of protein structural type via amino acid composition alone (Chou, Deleage and Roux; chapters 12
and 13); the prediction of secondary structure from amino acid sequence, naturally (Fasman et al.; chapters 6, 9, 10 and 13); and tertiary structure (Nagano, Cohen and Kuntz; chapters 11 and 17). The genetic information in contemporary organisms is derived from a process of shuffling of DNA sequences or structural domains, which implies constraints on amino acid combinations in the primary sequence (Doolittle; chapter 14). As one would expect, there are chapters dealing with electrostatic interactions (Rogers; chapter 8) hydrophobicity (Rose, Eisenberg; chapters 15 and 16) and their consequences for predictions of membrane protein structure (Janig, Stroud; chapters 18 and 19). Does this book accomplish what the editor set out to do? In the preface, Fasman states: “The prediction of the conformation of proteins has developed from an intellectual exercise into a serious practical endeavor that has great promise to yield new stable enzymes, products of pharmacological significance, and catalysts of great potential. With the application of prediction gaining momentum in various fields, such as enzymology and immunology. [this] volume is published to make available a thorough evaluation of present methods” (p. ix). In this, Fasman has not quite succeeded. This is exemplified by chapter 17 on tertiary structure prediction, in which Cohen and Kuntz show a model of interleukin-2. This model is in remarkable agreement with the structure published in December of 1987 (Brandhuber et al., Science 238,1707-1709,1987) to which no reference was made, which is suprising in a book on computer applications in today’s electronic typesetting environment. This is an encyclopedic compilation of how one takes advantage of the ever-expanding crystallographic structural data base to apply rules of protein stucture and folding to generate, from first principles, structures for proteins that are too large for NMR, too uncooperative to crystallize, or too scant, requiring analysis at the DNA level. Unfortunately, the mass of the book and the presentation make it difficult to read. It is a collection of reviews rather than a how-to book. One would have hoped for a demonstration of how the various algorithms predict known structures, but the most recent comparison of secondary structure predictions was from 1974 (p. 219). For membrane proteins, because we know the structures only for two light-driven prokaryotic systems, there is a catalog of predictions for which the reality of verification is not possible (pp. 274-276). The catalog lists references into 1987, so again it is not current. The detailed secondary-structure prediction compares only one protein, staphylococcal nuclease, with diffraction results (p. 402). Virtually all other comparisons are massive tables ot percentage correct, rather than along an amino acid sequence. One would like to see some of these predictive algorithms used with a structure for which there are many variants. An example might be T4 lysozyme, for which there is structural data with many variants and interesting similarities with avian lysozymes of known structure (Matthews, Nature 290, 334-335, 1981; Grutter et al., Nature 303, 828-830, 1983). Will the prediction algorithms applied to these independently known molecular structures converge? Alter-
May 16, 1990, Copyright
0 1990 by Cell Press
Book Reviews
Fertile Soil for Hemopoiesis Handbook of the Hemopoietic Microenvironment. Edited by M. Tavassoli. Clifton, New Jersey: Humana Press. (1989). 453 pp. $79.50.
The preface to this volume on the hemopoietic microenvironment contains a quotation made in 1918 by the Russian embryologist Vera Danchakoff that likens the bone marrow to a fertile soil in which the seed, in this case the hemopoietic stem cell, can develop. The aim of this volume is to describe what is known about the structure and function of the bone marrow environment. This is a timely undertaking because this specific area is rapidly evolving owing to the application of modern approaches in cell and molecular biology to its study. The term hemopoietic microenvironment is a catchall phrase that encompasses the cells, collectively referred to as stromal cells, and cell products, such as cytokines and extracellular matrix components, that form the supporting milieu for blood cell development. These microenvironmental elements are reviewed in 12 chapters, each written by a different author(s). The introductory chapter by Trentin provides a historical perspective of the field and an interesting discussion aimed at reconciling the long-debated issue of whether microenvironmental influences on stem cells are inductive or permissive. The remaining chapters address specific topics that include microenvironmental components, stromal cells in culture, interactions between stromal and hemopoietic cells, in vivo and in vitro methods to study the microenvironment, the extracellular matrix, and clinical applications. An excellent contribution for those just entering the field is the chapter by Lichtman and colleagues on bone marrow structure. This provides an overview of the medullary circulation, a summary of the different types of morphologically recognizable stromal cells and their spatial organization, and their relationship to hemopoietic cells. Additional portions of the book, such as the chapter by Tavassoli on adipocytes, deal in more detail with specific stromal cell types. If the definition of the hemopoietic microenvironment is taken to include any cell population that can influence hemopoiesis, then selected hemopoietic cells such as macrophages, natural killer (NK) cells, and T lymphocytes may also be considered to be constitutive elements. Reference to the role of macrophages is made throughout the book, and the effects of T cells and NK cells on human hemopoiesis are discussed in a chapter by Ascensao and Zanjani. However, the principal focus of the volume is on the sessile, connective tissue stromal cells. A major aim of workers in this field is to define the mechanisms by which stromal cells regulate hemopoiesis. The development of various long-term bone marrow culture systems can arbitrarily be chosen as marking the begin-
ning of the current era of research in this area. These cultures have in common the formation of a marrow-adherent layer in culture that apparently duplicates the environment present in the medullary cavity. Specific conditions have been developed by Dexter and colleagues and by Whitlock and Witte that permit the long-term production of myeloid or B lymphoid cells, respectively. The chapter by Quesenberry reviews these systems and how they have been used to study hemopoiesis in mice, humans, and other species, and a contribution by Shaklai compares the morphology of stromal cells grown in vitro to those observed in vivo. It is important to note that considerable efforts to dissect the hemopoietic microenvironment were made long before the advent of long-term cultures, and readers of the book will gain an appreciation for some of these experimental approaches, which include transplantation of cultured stromal cells or fresh marrow plugs to ectopic sites in vivo, in vivo microscopy, and the growth of hemopoietic cells on artificial membranes. Many laboratories have cloned stromal cells from the marrow or the adherent layers of long-term cultures; these have been of value in studies of particular environmental components and how these cells regulate blood cell production. The various stromal cell lines have been extensively characterized by phenotypic, morphologic, and biochemical means, as well as in functional assays in which their hemopoietic support capacity has been measured. The chapter by Quesenberry and another by Zipori provide an extensive review of some of the stromal cell lines, their characteristics, and how they have been used to study myelopoiesis and lymphopoiesis. Another topic of current interest is the study of the extracellular matrix (ECM). The role of the ECM in influencing cell migration, proliferation, and other developmental processes is now widely appreciated. The two informative chapters on the collagenous and noncollagenous ECM provide a background about the biochemistry of various matrix components, their distribution in fresh and cultured marrow, and how they may influence normal and dysregulated hemopoiesis. Because analysis of the hemopoietic system attracts investigators from multiple disciplines and new developments are rapid, it is difficult for a single review article, or even a book devoted to the topic, to address all relevant points or be completely up-to-date. Consequently, there are specific topics not discussed in detail in this volume. For example, stromal cells are known to be the source of multiple growth and differentiation factors. While many of these, particularly the colony-stimulating factors, are reviewed in the book, there has been progress in cloning additional stromal cell genes that encode novel hemopoietic factors, such as interleukin-7, a molecule that stimulates the proliferation of B cell progenitors. Another topic not addressed in detail is cytokine networks. As a result of their expression of various cytokine receptors, stromal cells are sensitive to conditions in their external milieu, and this can affect the types and level of factors secreted
Cell 558
by them. Additional rapidly evolving topics are the role of the ECM in binding hemopoietic cells of particular lineages and maturational states, and the binding of hemopoietic growth factors to ECM components. Complete, up-to-date information regarding the hemopoietic microenvironment will require the reading of this book in conjunction with more recent reviews and primary literature. However, this should not detract from strengths that include coverage of a wide range of topics, the presentation of a historical perspective of the field, and an easy-to-read format. In addition, the extensive reference lists at the end of most chapters provide a valuable bibliography. Kenneth Dorshkind Division of Biomedical Sciences University of California Riverside, California 92521
Protein Structural Clairvoyance Prediction of Protein Edited by New York:
of Protein Structure and Principles Conformation. G. D. Fasman. Plenum Press. (1989). 798 pp. $95.00.
With increasing frequency I get telephone calls or spontaneous visits from PCR-clone-sequence-site-specificmutagenize types who show me the predicted amino acid sequence from an open reading frame that has been entered into a packaged secondary-structure prediction algorithm. The question is, “Can you recommend an X-ray crystallographer or NMR spectroscopist to confirm my discovery that there is a zinc finger stuck in my leucine zipper?“Thus, this is a timely book which is required reading for all of us who deal with phenomena resulting from the interaction of biological macromolecules. Furthermore, as a public service a number of algorithms were collected and deposited at several national resources (appendix 2, p. 305). I will start with the bottom line-this will be a required text in our graduate-level course in biophysical chemistry. This does not imply that this is an excellent, well-written, or up-to-date book. What is important is that it addresses all the issues implied in the title. Students learn more from texts that are imperfect; instructors look better when the textbook deficiencies are obvious and easy to remedy. The subject builds on our training that the primary sequence of proteins determines the secondary structure, which in turn leads to tertiary structure and quaternary structure. Fasman has gathered most of the active workers in the field of protein structures, working on topics ranging from molecular dynamics (McCammon and Hagler; chapters 4 and 7) to protein crystallography (Richardsons, Deisenhofer, Stubbs; chapters l-3). There are chapters describing the prediction of protein structural type via amino acid composition alone (Chou, Deleage and Roux; chapters 12
and 13); the prediction of secondary structure from amino acid sequence, naturally (Fasman et al.; chapters 6, 9, 10 and 13); and tertiary structure (Nagano, Cohen and Kuntz; chapters 11 and 17). The genetic information in contemporary organisms is derived from a process of shuffling of DNA sequences or structural domains, which implies constraints on amino acid combinations in the primary sequence (Doolittle; chapter 14). As one would expect, there are chapters dealing with electrostatic interactions (Rogers; chapter 8) hydrophobicity (Rose, Eisenberg; chapters 15 and 16) and their consequences for predictions of membrane protein structure (Janig, Stroud; chapters 18 and 19). Does this book accomplish what the editor set out to do? In the preface, Fasman states: “The prediction of the conformation of proteins has developed from an intellectual exercise into a serious practical endeavor that has great promise to yield new stable enzymes, products of pharmacological significance, and catalysts of great potential. With the application of prediction gaining momentum in various fields, such as enzymology and immunology. [this] volume is published to make available a thorough evaluation of present methods” (p. ix). In this, Fasman has not quite succeeded. This is exemplified by chapter 17 on tertiary structure prediction, in which Cohen and Kuntz show a model of interleukin-2. This model is in remarkable agreement with the structure published in December of 1987 (Brandhuber et al., Science 238,1707-1709,1987) to which no reference was made, which is suprising in a book on computer applications in today’s electronic typesetting environment. This is an encyclopedic compilation of how one takes advantage of the ever-expanding crystallographic structural data base to apply rules of protein stucture and folding to generate, from first principles, structures for proteins that are too large for NMR, too uncooperative to crystallize, or too scant, requiring analysis at the DNA level. Unfortunately, the mass of the book and the presentation make it difficult to read. It is a collection of reviews rather than a how-to book. One would have hoped for a demonstration of how the various algorithms predict known structures, but the most recent comparison of secondary structure predictions was from 1974 (p. 219). For membrane proteins, because we know the structures only for two light-driven prokaryotic systems, there is a catalog of predictions for which the reality of verification is not possible (pp. 274-276). The catalog lists references into 1987, so again it is not current. The detailed secondary-structure prediction compares only one protein, staphylococcal nuclease, with diffraction results (p. 402). Virtually all other comparisons are massive tables ot percentage correct, rather than along an amino acid sequence. One would like to see some of these predictive algorithms used with a structure for which there are many variants. An example might be T4 lysozyme, for which there is structural data with many variants and interesting similarities with avian lysozymes of known structure (Matthews, Nature 290, 334-335, 1981; Grutter et al., Nature 303, 828-830, 1983). Will the prediction algorithms applied to these independently known molecular structures converge? Alter-