Hematopoietic cytokines, transcription factors and lineage commitment

Abstract

The past two decades have witnessed signi®cant advances in our understanding of the cellular physiology and molecular regulation of hematopoiesis. At the heart of stem cell self-renewal and lineage commitment decisions lies the relative expression levels of lineage-speci®c transcription factors. The expression of these transcription factors in early stem cells may be promiscuous and uctuate, but ultimately comes under the in¯uence of extracellular regulatory signals in the form of hematopoietic cytokines. In this review, we ®rst summarize our current understanding of the phenotypic characterization of hematopoietic stem cells. Next, we describe key known transcription factors which govern stem cell selfrenewal and lineage commitment decisions. Finally, we review data concerning the role of speci®c cytokines in in¯uencing these decisions. From this review, a picture emerges in which stem cell fate decisions are governed by the integrated e ects of intrinsic transcription factors and external signaling pathways initiated by regulatory cytokines.

E2a/Pbx1 oncogene inhibits terminal differentiation but not myeloid potential of pro-T cells

“…At the molecular level, stem cell fate decisions are governed by the integrated effects of intrinsic transcription factors and external signaling pathways initiated by regulatory growth factors or cytokines (Zhu and Emerson, 2002). Alterations of these pathways cause the dysregulated differentiation and genetic instability in myeloproliferative disorders and leukemia.…”

The GOD of Hematopoietic Stem Cells: A Clonal Diversity Model of the Stem Cell Compartment

“…54 HSC (analyzed as a population) show open chromatin configurations for lineage specific genes and HSC seem to express lineage specific genes promiscuously. [54][55][56][57] Differentiation is accompanied by the expression of genes, such as Pax5, that suppress genes needed for the development into other lineages. 58 There is evidence that removing or interfering with epigenetic imprinting will protect HSC maintenance, even if the culture conditions favor differentiation.…”

Regulation of FLT3 and its ligand in normal hematopoietic progenitor cells

“…Hematopoiesis is a complex process in which survival, proliferation, differentiation, and other functions are at least partially regulated through a network of growth factors [1,[31][32][33]. FLT3 and its ligand FL are known regulators in this process, mainly enhancing effects of other cytokines more than having specific effects by itself.…”