Cell-fate conversion of lymphoid-committed progenitors by instructive actions of cytokines
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...
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| Veröffentlicht in: | Nature (London) 2000-09, Vol.407 (6802), p.383-386 |
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| creator | Kondo, Motonari Scherer, David C Miyamoto, Toshihiro King, Angela G Akashi, Koichi Sugamura, Kazuo Weissman, Irving L |
| description | 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. |
| doi_str_mv | 10.1038/35030112 |
| format | Article |
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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.</description><identifier>ISSN: 0028-0836</identifier><identifier>EISSN: 1476-4687</identifier><identifier>DOI: 10.1038/35030112</identifier><identifier>PMID: 11014194</identifier><identifier>CODEN: NATUAS</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>Animals ; Biological and medical sciences ; Bone marrow ; Cell Lineage - physiology ; Cells, Cultured ; Cellular biology ; Clone Cells ; Cytokines - physiology ; Fundamental and applied biological sciences. Psychology ; Fundamental immunology ; Granulocyte-Macrophage Colony-Stimulating Factor - physiology ; Hematopoietic Stem Cells ; Humanities and Social Sciences ; Humans ; Immunobiology ; letter ; Leukopoiesis ; Lymphatic system ; Lymphocytes ; Lymphoid cells: ontogeny, maturation, markers, receptors, circulation and recirculation ; Lymphoid Tissue - cytology ; Mice ; Mice, Transgenic ; multidisciplinary ; Receptors, Interleukin-2 - physiology ; Science ; Science (multidisciplinary) ; Signal Transduction ; Stem cells</subject><ispartof>Nature (London), 2000-09, Vol.407 (6802), p.383-386</ispartof><rights>Macmillan Magazines Ltd. 2000</rights><rights>2000 INIST-CNRS</rights><rights>COPYRIGHT 2000 Nature Publishing Group</rights><rights>Copyright Macmillan Journals Ltd. Sep 21, 2000</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c728t-7f2abf808bb907ccc56a72ca9d2e2c16215a123a571b1ad6aa86744ef2b9cbd13</citedby><cites>FETCH-LOGICAL-c728t-7f2abf808bb907ccc56a72ca9d2e2c16215a123a571b1ad6aa86744ef2b9cbd13</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1038/35030112$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1038/35030112$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,778,782,27911,27912,41475,42544,51306</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=1476885$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/11014194$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kondo, Motonari</creatorcontrib><creatorcontrib>Scherer, David C</creatorcontrib><creatorcontrib>Miyamoto, Toshihiro</creatorcontrib><creatorcontrib>King, Angela G</creatorcontrib><creatorcontrib>Akashi, Koichi</creatorcontrib><creatorcontrib>Sugamura, Kazuo</creatorcontrib><creatorcontrib>Weissman, Irving L</creatorcontrib><title>Cell-fate conversion of lymphoid-committed progenitors by instructive actions of cytokines</title><title>Nature (London)</title><addtitle>Nature</addtitle><addtitle>Nature</addtitle><description>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.</description><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Bone marrow</subject><subject>Cell Lineage - physiology</subject><subject>Cells, Cultured</subject><subject>Cellular biology</subject><subject>Clone Cells</subject><subject>Cytokines - physiology</subject><subject>Fundamental and applied biological sciences. 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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.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>11014194</pmid><doi>10.1038/35030112</doi><tpages>4</tpages></addata></record> |
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| ispartof | Nature (London), 2000-09, Vol.407 (6802), p.383-386 |
| issn | 0028-0836 1476-4687 |
| language | eng |
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| source | MEDLINE; Springer Nature - Complete Springer Journals; Nature Journals Online |
| subjects | Animals Biological and medical sciences Bone marrow Cell Lineage - physiology Cells, Cultured Cellular biology Clone Cells Cytokines - physiology Fundamental and applied biological sciences. Psychology Fundamental immunology Granulocyte-Macrophage Colony-Stimulating Factor - physiology Hematopoietic Stem Cells Humanities and Social Sciences Humans Immunobiology letter Leukopoiesis Lymphatic system Lymphocytes Lymphoid cells: ontogeny, maturation, markers, receptors, circulation and recirculation Lymphoid Tissue - cytology Mice Mice, Transgenic multidisciplinary Receptors, Interleukin-2 - physiology Science Science (multidisciplinary) Signal Transduction Stem cells |
| title | Cell-fate conversion of lymphoid-committed progenitors by instructive actions of cytokines |
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