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, Irving L. Weissman

Research output: Contribution to journalArticlepeer-review

309 Citations (Scopus)

Abstract

The primary role of cytokines in haemato-lymphopoiesis is thought to be the regulation of cell growth and survival1-3. 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 myelomonocytic 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 crirical step in lymphoid commitment is downregulation of cytokine receptors that drive myeloid cell development.

Original languageEnglish
Pages (from-to)383-386
Number of pages4
JournalNature
Volume407
Issue number6802
DOIs
Publication statusPublished - Sep 21 2000
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • General

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