Transcription Factors Regulating Early Hematopoietic Development and Lineage Commitment

  • Stuart H. Orkin
Part of the Contemporary Immunology book series (CONTIM)


The establishment of the hematopoietic system entails a series of developmental decisions, followed by expansion of immature progenitors or hematopoietic stem cells (HSCs) and the subsequent commitment of later progenitors to differentiation along selected lineages (1). Within the early embryo, ventral (or posterior) mesoderm gives rise to presumptive hemangioblasts (2) that are further specified to embryonic erythroid precursors and vascular cells in the developing yolk sac blood islands (Fig. 1). Later, intraembryonic hematopoiesis occurs in the fetal liver, most likely seeded from progenitors or HSCs located in the aortic/gonad/mesonephros (AGM) region (3–6). In addition to these important developmental decisions, amplification of hematopoietic progenitors within the yolk sac and embryonic compartments is necessary to provide the total number of cells required to meet increasing demands as the embryo grows. Various inductive events under the control of growth factors presumably lead to the origin of the hemangioblast, the specification of embryonic hematopoiesis, and the appearance of HSCs in the AGM region. The critical developmental decisions are thought to be executed by transcription factors, functioning in a combinatorial manner. These are the subject of this review. Genetic approaches have culminated in the identification of several transcription factors, or transcription factor associated proteins that are essential for various aspects of hematopoietic development. Examples are discussed below with the aim of defining some principles underlying hematopoietic development. The factors reviewed herein are summarized in Table 1 and are individually considered throughout the chapter.


Embryonic Stem Cell Erythroid Differentiation Hematopoietic Lineage Erythroid Precursor Hematopoietic Development 
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  • Stuart H. Orkin

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