Bone marrow CD169+ macrophages promote the retention of hematopoietic stem and progenitor cells in the mesenchymal stem cell niche
Hematopoietic stem cells (HSCs) reside in specialized bone marrow (BM) niches regulated by the sympathetic nervous system (SNS). Here, we have examined whether mononuclear phagocytes modulate the HSC niche. We defined three populations of BM mononuclear phagocytes that include Gr-1(hi) monocytes (MO...
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| Veröffentlicht in: | The Journal of experimental medicine 2011-02, Vol.208 (2), p.261-271 |
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| creator | Chow, Andrew Lucas, Daniel Hidalgo, Andrés Méndez-Ferrer, Simón Hashimoto, Daigo Scheiermann, Christoph Battista, Michela Leboeuf, Marylene Prophete, Colette van Rooijen, Nico Tanaka, Masato Merad, Miriam Frenette, Paul S |
| description | Hematopoietic stem cells (HSCs) reside in specialized bone marrow (BM) niches regulated by the sympathetic nervous system (SNS). Here, we have examined whether mononuclear phagocytes modulate the HSC niche. We defined three populations of BM mononuclear phagocytes that include Gr-1(hi) monocytes (MOs), Gr-1(lo) MOs, and macrophages (MΦ) based on differential expression of Gr-1, CD115, F4/80, and CD169. Using MO and MΦ conditional depletion models, we found that reductions in BM mononuclear phagocytes led to reduced BM CXCL12 levels, the selective down-regulation of HSC retention genes in Nestin(+) niche cells, and egress of HSCs/progenitors to the bloodstream. Furthermore, specific depletion of CD169(+) MΦ, which spares BM MOs, was sufficient to induce HSC/progenitor egress. MΦ depletion also enhanced mobilization induced by a CXCR4 antagonist or granulocyte colony-stimulating factor. These results highlight two antagonistic, tightly balanced pathways that regulate maintenance of HSCs/progenitors in the niche during homeostasis, in which MΦ cross talk with the Nestin(+) niche cell promotes retention, and in contrast, SNS signals enhance egress. Thus, strategies that target BM MΦ hold the potential to augment stem cell yields in patients that mobilize HSCs/progenitors poorly. |
| doi_str_mv | 10.1084/jem.20101688 |
| format | Article |
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Here, we have examined whether mononuclear phagocytes modulate the HSC niche. We defined three populations of BM mononuclear phagocytes that include Gr-1(hi) monocytes (MOs), Gr-1(lo) MOs, and macrophages (MΦ) based on differential expression of Gr-1, CD115, F4/80, and CD169. Using MO and MΦ conditional depletion models, we found that reductions in BM mononuclear phagocytes led to reduced BM CXCL12 levels, the selective down-regulation of HSC retention genes in Nestin(+) niche cells, and egress of HSCs/progenitors to the bloodstream. Furthermore, specific depletion of CD169(+) MΦ, which spares BM MOs, was sufficient to induce HSC/progenitor egress. MΦ depletion also enhanced mobilization induced by a CXCR4 antagonist or granulocyte colony-stimulating factor. These results highlight two antagonistic, tightly balanced pathways that regulate maintenance of HSCs/progenitors in the niche during homeostasis, in which MΦ cross talk with the Nestin(+) niche cell promotes retention, and in contrast, SNS signals enhance egress. Thus, strategies that target BM MΦ hold the potential to augment stem cell yields in patients that mobilize HSCs/progenitors poorly.</description><identifier>ISSN: 0022-1007</identifier><identifier>EISSN: 1540-9538</identifier><identifier>DOI: 10.1084/jem.20101688</identifier><identifier>PMID: 21282381</identifier><language>eng</language><publisher>United States: The Rockefeller University Press</publisher><subject>Animals ; Bone Marrow Cells - cytology ; Bone Marrow Cells - metabolism ; Chemokine CXCL12 - metabolism ; Colony-Forming Units Assay ; DNA Primers - genetics ; Enzyme-Linked Immunosorbent Assay ; Flow Cytometry ; Fluorescent Antibody Technique ; Hematopoietic Stem Cell Mobilization ; Hematopoietic Stem Cells - cytology ; Homeostasis - immunology ; Interleukin-10 - genetics ; Macrophages - metabolism ; Male ; Membrane Glycoproteins - metabolism ; Mesenchymal Stromal Cells - cytology ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Monocytes - metabolism ; Polymerase Chain Reaction ; Receptor Cross-Talk - immunology ; Receptors, Immunologic - metabolism ; Sialic Acid Binding Ig-like Lectin 1</subject><ispartof>The Journal of experimental medicine, 2011-02, Vol.208 (2), p.261-271</ispartof><rights>2011 Chow et al. 2011</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c594t-3b757c2f11e6825762d679e8899c09c18a508fe9f07b55212632aeff0c4ebb8e3</citedby><cites>FETCH-LOGICAL-c594t-3b757c2f11e6825762d679e8899c09c18a508fe9f07b55212632aeff0c4ebb8e3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,776,780,881,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21282381$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Chow, Andrew</creatorcontrib><creatorcontrib>Lucas, Daniel</creatorcontrib><creatorcontrib>Hidalgo, Andrés</creatorcontrib><creatorcontrib>Méndez-Ferrer, Simón</creatorcontrib><creatorcontrib>Hashimoto, Daigo</creatorcontrib><creatorcontrib>Scheiermann, Christoph</creatorcontrib><creatorcontrib>Battista, Michela</creatorcontrib><creatorcontrib>Leboeuf, Marylene</creatorcontrib><creatorcontrib>Prophete, Colette</creatorcontrib><creatorcontrib>van Rooijen, Nico</creatorcontrib><creatorcontrib>Tanaka, Masato</creatorcontrib><creatorcontrib>Merad, Miriam</creatorcontrib><creatorcontrib>Frenette, Paul S</creatorcontrib><title>Bone marrow CD169+ macrophages promote the retention of hematopoietic stem and progenitor cells in the mesenchymal stem cell niche</title><title>The Journal of experimental medicine</title><addtitle>J Exp Med</addtitle><description>Hematopoietic stem cells (HSCs) reside in specialized bone marrow (BM) niches regulated by the sympathetic nervous system (SNS). Here, we have examined whether mononuclear phagocytes modulate the HSC niche. We defined three populations of BM mononuclear phagocytes that include Gr-1(hi) monocytes (MOs), Gr-1(lo) MOs, and macrophages (MΦ) based on differential expression of Gr-1, CD115, F4/80, and CD169. Using MO and MΦ conditional depletion models, we found that reductions in BM mononuclear phagocytes led to reduced BM CXCL12 levels, the selective down-regulation of HSC retention genes in Nestin(+) niche cells, and egress of HSCs/progenitors to the bloodstream. Furthermore, specific depletion of CD169(+) MΦ, which spares BM MOs, was sufficient to induce HSC/progenitor egress. MΦ depletion also enhanced mobilization induced by a CXCR4 antagonist or granulocyte colony-stimulating factor. These results highlight two antagonistic, tightly balanced pathways that regulate maintenance of HSCs/progenitors in the niche during homeostasis, in which MΦ cross talk with the Nestin(+) niche cell promotes retention, and in contrast, SNS signals enhance egress. Thus, strategies that target BM MΦ hold the potential to augment stem cell yields in patients that mobilize HSCs/progenitors poorly.</description><subject>Animals</subject><subject>Bone Marrow Cells - cytology</subject><subject>Bone Marrow Cells - metabolism</subject><subject>Chemokine CXCL12 - metabolism</subject><subject>Colony-Forming Units Assay</subject><subject>DNA Primers - genetics</subject><subject>Enzyme-Linked Immunosorbent Assay</subject><subject>Flow Cytometry</subject><subject>Fluorescent Antibody Technique</subject><subject>Hematopoietic Stem Cell Mobilization</subject><subject>Hematopoietic Stem Cells - cytology</subject><subject>Homeostasis - immunology</subject><subject>Interleukin-10 - genetics</subject><subject>Macrophages - metabolism</subject><subject>Male</subject><subject>Membrane Glycoproteins - metabolism</subject><subject>Mesenchymal Stromal Cells - cytology</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Mice, Knockout</subject><subject>Monocytes - metabolism</subject><subject>Polymerase Chain Reaction</subject><subject>Receptor Cross-Talk - immunology</subject><subject>Receptors, Immunologic - metabolism</subject><subject>Sialic Acid Binding Ig-like Lectin 1</subject><issn>0022-1007</issn><issn>1540-9538</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkTtvFDEURi0EIkugo0buKGCCH-NXgwTLU4pEA7Xl8d7ZcTRjD7YXlJZfjpdNIqioLOsef_K5H0JPKbmgRPevrmC5YIQSKrW-hzZU9KQzguv7aEMIYx0lRJ2hR6VcEUL7XsiH6IxRphnXdIN-vU0R8OJyTj_x9h2V5kW7-ZzWye2h4DWnJVXAdQKcoUKsIUWcRjzB4mpaU4AaPC4VFuzi7sjvIYaaMvYwzwWH-OftAgWin64XN5_g4xTH4Cd4jB6Mbi7w5OY8R98-vP-6_dRdfvn4efvmsvPC9LXjgxLKs5FSkJoJJdlOKgNaG-OJ8VQ7QfQIZiRqEKIZSs4cjCPxPQyDBn6OXp9y18OwwM43l-xmu-bQ9K9tcsH-O4lhsvv0w3LCjRaiBTy_Ccjp-wFKtUsoRw8XIR2KNURRoaXq_0tqQQ2XXMlGvjyRbeWlZBjv_kOJPfZrW7_2tt-GP_vb4Q6-LZT_BiV5oyo</recordid><startdate>20110214</startdate><enddate>20110214</enddate><creator>Chow, Andrew</creator><creator>Lucas, Daniel</creator><creator>Hidalgo, Andrés</creator><creator>Méndez-Ferrer, Simón</creator><creator>Hashimoto, Daigo</creator><creator>Scheiermann, Christoph</creator><creator>Battista, Michela</creator><creator>Leboeuf, Marylene</creator><creator>Prophete, Colette</creator><creator>van Rooijen, Nico</creator><creator>Tanaka, Masato</creator><creator>Merad, Miriam</creator><creator>Frenette, Paul S</creator><general>The Rockefeller University Press</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>7T5</scope><scope>H94</scope><scope>5PM</scope></search><sort><creationdate>20110214</creationdate><title>Bone marrow CD169+ macrophages promote the retention of hematopoietic stem and progenitor cells in the mesenchymal stem cell niche</title><author>Chow, Andrew ; Lucas, Daniel ; Hidalgo, Andrés ; Méndez-Ferrer, Simón ; Hashimoto, Daigo ; Scheiermann, Christoph ; Battista, Michela ; Leboeuf, Marylene ; Prophete, Colette ; van Rooijen, Nico ; Tanaka, Masato ; Merad, Miriam ; Frenette, Paul S</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c594t-3b757c2f11e6825762d679e8899c09c18a508fe9f07b55212632aeff0c4ebb8e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>Animals</topic><topic>Bone Marrow Cells - cytology</topic><topic>Bone Marrow Cells - metabolism</topic><topic>Chemokine CXCL12 - metabolism</topic><topic>Colony-Forming Units Assay</topic><topic>DNA Primers - genetics</topic><topic>Enzyme-Linked Immunosorbent Assay</topic><topic>Flow Cytometry</topic><topic>Fluorescent Antibody Technique</topic><topic>Hematopoietic Stem Cell Mobilization</topic><topic>Hematopoietic Stem Cells - cytology</topic><topic>Homeostasis - immunology</topic><topic>Interleukin-10 - genetics</topic><topic>Macrophages - metabolism</topic><topic>Male</topic><topic>Membrane Glycoproteins - metabolism</topic><topic>Mesenchymal Stromal Cells - cytology</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Mice, Knockout</topic><topic>Monocytes - metabolism</topic><topic>Polymerase Chain Reaction</topic><topic>Receptor Cross-Talk - immunology</topic><topic>Receptors, Immunologic - metabolism</topic><topic>Sialic Acid Binding Ig-like Lectin 1</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Chow, Andrew</creatorcontrib><creatorcontrib>Lucas, Daniel</creatorcontrib><creatorcontrib>Hidalgo, Andrés</creatorcontrib><creatorcontrib>Méndez-Ferrer, Simón</creatorcontrib><creatorcontrib>Hashimoto, Daigo</creatorcontrib><creatorcontrib>Scheiermann, Christoph</creatorcontrib><creatorcontrib>Battista, Michela</creatorcontrib><creatorcontrib>Leboeuf, Marylene</creatorcontrib><creatorcontrib>Prophete, Colette</creatorcontrib><creatorcontrib>van Rooijen, Nico</creatorcontrib><creatorcontrib>Tanaka, Masato</creatorcontrib><creatorcontrib>Merad, Miriam</creatorcontrib><creatorcontrib>Frenette, Paul S</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>Immunology Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>The Journal of experimental medicine</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Chow, Andrew</au><au>Lucas, Daniel</au><au>Hidalgo, Andrés</au><au>Méndez-Ferrer, Simón</au><au>Hashimoto, Daigo</au><au>Scheiermann, Christoph</au><au>Battista, Michela</au><au>Leboeuf, Marylene</au><au>Prophete, Colette</au><au>van Rooijen, Nico</au><au>Tanaka, Masato</au><au>Merad, Miriam</au><au>Frenette, Paul S</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Bone marrow CD169+ macrophages promote the retention of hematopoietic stem and progenitor cells in the mesenchymal stem cell niche</atitle><jtitle>The Journal of experimental medicine</jtitle><addtitle>J Exp Med</addtitle><date>2011-02-14</date><risdate>2011</risdate><volume>208</volume><issue>2</issue><spage>261</spage><epage>271</epage><pages>261-271</pages><issn>0022-1007</issn><eissn>1540-9538</eissn><abstract>Hematopoietic stem cells (HSCs) reside in specialized bone marrow (BM) niches regulated by the sympathetic nervous system (SNS). Here, we have examined whether mononuclear phagocytes modulate the HSC niche. We defined three populations of BM mononuclear phagocytes that include Gr-1(hi) monocytes (MOs), Gr-1(lo) MOs, and macrophages (MΦ) based on differential expression of Gr-1, CD115, F4/80, and CD169. Using MO and MΦ conditional depletion models, we found that reductions in BM mononuclear phagocytes led to reduced BM CXCL12 levels, the selective down-regulation of HSC retention genes in Nestin(+) niche cells, and egress of HSCs/progenitors to the bloodstream. Furthermore, specific depletion of CD169(+) MΦ, which spares BM MOs, was sufficient to induce HSC/progenitor egress. MΦ depletion also enhanced mobilization induced by a CXCR4 antagonist or granulocyte colony-stimulating factor. These results highlight two antagonistic, tightly balanced pathways that regulate maintenance of HSCs/progenitors in the niche during homeostasis, in which MΦ cross talk with the Nestin(+) niche cell promotes retention, and in contrast, SNS signals enhance egress. Thus, strategies that target BM MΦ hold the potential to augment stem cell yields in patients that mobilize HSCs/progenitors poorly.</abstract><cop>United States</cop><pub>The Rockefeller University Press</pub><pmid>21282381</pmid><doi>10.1084/jem.20101688</doi><tpages>11</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Animals Bone Marrow Cells - cytology Bone Marrow Cells - metabolism Chemokine CXCL12 - metabolism Colony-Forming Units Assay DNA Primers - genetics Enzyme-Linked Immunosorbent Assay Flow Cytometry Fluorescent Antibody Technique Hematopoietic Stem Cell Mobilization Hematopoietic Stem Cells - cytology Homeostasis - immunology Interleukin-10 - genetics Macrophages - metabolism Male Membrane Glycoproteins - metabolism Mesenchymal Stromal Cells - cytology Mice Mice, Inbred C57BL Mice, Knockout Monocytes - metabolism Polymerase Chain Reaction Receptor Cross-Talk - immunology Receptors, Immunologic - metabolism Sialic Acid Binding Ig-like Lectin 1 |
| title | Bone marrow CD169+ macrophages promote the retention of hematopoietic stem and progenitor cells in the mesenchymal stem cell niche |
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