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1 - A Developmental Approach to Hematopoiesis

from SECTION ONE - THE MOLECULAR, CELLULAR, AND GENETIC BASIS OF HEMOGLOBIN DISORDERS

Published online by Cambridge University Press:  03 May 2010

Martin H. Steinberg ,
Bernard G. Forget ,
Douglas R. Higgs  and
David J. Weatherall
By
Elaine Dzierzak
Martin H. Steinberg
Affiliation:
Boston University
Bernard G. Forget
Affiliation:
Yale University, Connecticut
Douglas R. Higgs
Affiliation:
MRC Institute of Molecular Medicine, University of Oxford
David J. Weatherall
Affiliation:
Albert Einstein College of Medicine, New York
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Summary

INTRODUCTION AND GENERAL CONSIDERATIONS

During mammalian development, the first morphologically recognizable blood cells in the conceptus are those of the erythroid lineage. The early production of erythroid lineage cells in the yolk sac is required for the development of the vertebrate embryo. These blood cells are short-lived, however. In contrast, long-term adult hematopoiesis results from a complex cell lineage differentiation hierarchy that produces at least eight functionally distinct lineages of differentiated blood cells. The founder cells for this hierarchy are the hematopoietic stem cells (HSCs), which undergo progressive differentiation, proliferation, and restriction in lineage potential. The adult blood system is constantly replenished throughout adult life from rare HSCs harbored in the bone marrow. The field of “developmental hematopoiesis” investigates how this complex adult system is generated in the conceptus. Current research interests in this field include 1) the embryonic origins, cell lineage relationships, and functions of the cells within the multiple embryonic hematopoietic compartments; 2) the changing developmental microenvironments that support hematopoietic (stem) cell growth; and 3) the molecular programming of the hematopoietic system during ontogeny. This chapter will focus on our current knowledge concerning the embryonic beginnings of the adult hematopoietic system. Insights emerging from such a developmental approach should lead to novel molecular and cellular manipulations that could aid in the ex vivo generation and/or expansion of HSCs and progenitors for clinical use in transplantations for leukemias or blood-related genetic disease.

Type
Chapter
Information
Disorders of Hemoglobin
Genetics, Pathophysiology, and Clinical Management
 , pp. 3 - 23
Publisher: Cambridge University Press
Print publication year: 2009

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