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

M Kondo, DC Scherer, T Miyamoto, AG King, K Akashi… - Nature, 2000 - nature.com
M Kondo, DC Scherer, T Miyamoto, AG King, K Akashi, K Sugamura, IL Weissman
Nature, 2000nature.com
The primary role of cytokines in haemato-lymphopoiesis is thought to be the regulation of
cell growth and survival,,. But the instructive action of cytokines in haematopoiesis has not
been well addressed. Here we show that a clonogenic common lymphoid progenitor, 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) …
Abstract
The primary role of cytokines in haemato-lymphopoiesis is thought to be the regulation of cell growth and survival,,. But the instructive action of cytokines in haematopoiesis has not been well addressed. Here we show that a clonogenic common lymphoid progenitor, 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.
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