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Diversification of haematopoietic stem cells to specific lineages

Nature Reviews Genetics volume 1, pages 57–64 (2000)Cite this article

Abstract

Diverse types of blood cell (lineages) are produced from rare haematopoietic stem cells that reside in the bone marrow. This process, known as haematopoiesis, provides a valuable model for examining how genetic programs are established and executed in vertebrates, and also how homeostasis of blood formation is altered in leukaemias. So, how does an apparently small group of critical lineage-restricted nuclear regulatory factors specify the diversity of haematopoietic cells? Recent findings not only indicate how this may be achieved but also show the extraordinary plasticity of tissue stem cells in vivo.

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Figure 1: Schematic view of adult haematopoiesis.
Figure 2: Proposed interactions between GATA-1, FOG-1 and PU.1, and their respective effects on gene regulation.
Figure 3: Regulatory interactions of key lineage-specific factors in cell type specification.

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Acknowledgements

Owing to space constraints it has not been possible to cite all relevant publications. I especially thank those investigators who generously communicated findings before publication. S.H.O. is an investigator of the Howard Hughes Medical Institute.

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  1. Division of Hematology, Children's Hospital, 300 Longwood Avenue, Boston, 02115, Massachusetts, USA

    Stuart H. Orkin

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DATABASE LINKS

BMP-4

runx1

myb

ets

GATA-1

GATA-2

GATA-3

MafB

serpent

lozenge

Pax5

T-bet

IL-4

IFNγ

Spi-1

Ikaros

Groucho

myoD

SCL/tal-1

Tel

C/EBP

E2A

FURTHER INFORMATION

Stem cell database

Stuart Orkin's research interests

Encyclopedia of life sciences article entitled Blood cell: lineage restriction

Glossary

HAEMATOPOIETIC STEM CELL

Cell that upon transplantation to an appropriately conditioned recipient reconstitutes the entire haematopoietic system.

MESODERM

Third germ layer in the embryo, formed during the process of gastrulation.

BLOOD ISLANDS

Structures in the extraembryonic yolk sac, composed of endothelial cells, primitive erythrocytes and underlying endoderm.

HAEMANGIOBLAST

Cell which is bipotential for vascular and haematopoietic development.

ENDOTHELIAL CELL

Vascular cell.

ZINC-FINGER

Protein module in which cysteine or cysteine-histidine residues coordinate a zinc ion. Zinc-fingers are often used in DNA recognition and also in protein–protein interactions.

B-ZIPPER

Class of transcription factors in which a basic domain involved in DNA recognition neighbours a region of repeating hydrophobic amino acids that mediate protein dimerization. Members include c-Jun, C/EBP and myogenic factors.

CYTOKINES

Polypeptide haematopoietic regulatory factors, such as erythropoietin and colony-stimulating factors.

AUTOREGULATION

Positive feedback regulation by a transcription factor on expression from its own gene.

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Orkin, S. Diversification of haematopoietic stem cells to specific lineages. Nat Rev Genet 1, 57–64 (2000). https://doi.org/10.1038/35049577

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