Cell-fate conversion of lymphoid-committed progenitors by instructive actions of cytokines

Motonari Kondo (), David C. Scherer, Toshihiro Miyamoto, Angela G. King, Koichi Akashi, Kazuo Sugamura and Irving L. Weissman
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Motonari Kondo: Stanford University School of Medicine
David C. Scherer: Stanford University School of Medicine
Toshihiro Miyamoto: Stanford University School of Medicine
Angela G. King: Stanford University School of Medicine
Koichi Akashi: Stanford University School of Medicine
Kazuo Sugamura: Department of Microbiology and Immunology Tohoku University School of Medicine
Irving L. Weissman: Stanford University School of Medicine

Nature, 2000, vol. 407, issue 6802, 383-386

Abstract: Abstract The primary role of cytokines in haemato-lymphopoiesis is thought to be the regulation of cell growth and survival1,2,3. But the instructive action of cytokines in haematopoiesis has not been well addressed4. Here we show that a clonogenic common lymphoid progenitor5, a bone marrow-resident cell that gives rise exclusively to lymphocytes (T, B and natural killer cells), can be redirected to the myeloid lineage by stimulation through exogenously expressed interleukin (IL)-2 and GM-CSF (granulocyte/macrophage colony-stimulating factor) receptors. Analysis of mutants of the β-chain of the IL-2 receptor revealed that the granulocyte- and monocyte-differentiation signals are triggered by different cytoplasmic domains, showing that the signalling pathway(s) responsible for these unique developmental outcomes are separable. Finally, we show that the endogenous myelo-monocytic cytokine receptors for GM-CSF and macrophage colony-stimulating factor (M-CSF) are expressed at low to moderate levels on the more primitive haematopoietic stem cells, are absent on common lymphoid progenitors, and are upregulated after myeloid lineage induction by IL-2. We conclude that cytokine signalling can regulate cell-fate decisions and propose that a critical step in lymphoid commitment is downregulation of cytokine receptors that drive myeloid cell development.

Date: 2000
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DOI: 10.1038/35030112

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