The transcription factor NR4A1 (Nur77) controls bone marrow differentiation and the survival of Ly6C− monocytes
Ly6C – monocytes patrol blood vessels by crawling along uninflamed vasculature. Hedrick and colleagues show that the transcription factor NR4A1 is required for the development and survival of Ly6C – monocytes. The transcription factors that regulate differentiation into the monocyte subset in bone m...
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| Veröffentlicht in: | Nature immunology 2011-07, Vol.12 (8), p.778-785 |
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| creator | Hanna, Richard N Carlin, Leo M Hubbeling, Harper G Nackiewicz, Dominika Green, Angela M Punt, Jennifer A Geissmann, Frederic Hedrick, Catherine C |
| description | Ly6C
–
monocytes patrol blood vessels by crawling along uninflamed vasculature. Hedrick and colleagues show that the transcription factor NR4A1 is required for the development and survival of Ly6C
–
monocytes.
The transcription factors that regulate differentiation into the monocyte subset in bone marrow have not yet been identified. Here we found that the orphan nuclear receptor NR4A1 controlled the differentiation of Ly6C
−
monocytes. Ly6C
−
monocytes, which function in a surveillance role in circulation, were absent from
Nr4a1
−/−
mice. Normal numbers of myeloid progenitor cells were present in
Nr4a1
−/−
mice, which indicated that the defect occurred during later stages of monocyte development. The defect was cell intrinsic, as wild-type mice that received bone marrow from
Nr4a1
−/−
mice developed fewer patrolling monocytes than did recipients of wild-type bone marrow. The Ly6C
−
monocytes remaining in the bone marrow of
Nr4a1
−/−
mice were arrested in S phase of the cell cycle and underwent apoptosis. Thus, NR4A1 functions as a master regulator of the differentiation and survival of 'patrolling' Ly6C
−
monocytes. |
| doi_str_mv | 10.1038/ni.2063 |
| format | Article |
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–
monocytes patrol blood vessels by crawling along uninflamed vasculature. Hedrick and colleagues show that the transcription factor NR4A1 is required for the development and survival of Ly6C
–
monocytes.
The transcription factors that regulate differentiation into the monocyte subset in bone marrow have not yet been identified. Here we found that the orphan nuclear receptor NR4A1 controlled the differentiation of Ly6C
−
monocytes. Ly6C
−
monocytes, which function in a surveillance role in circulation, were absent from
Nr4a1
−/−
mice. Normal numbers of myeloid progenitor cells were present in
Nr4a1
−/−
mice, which indicated that the defect occurred during later stages of monocyte development. The defect was cell intrinsic, as wild-type mice that received bone marrow from
Nr4a1
−/−
mice developed fewer patrolling monocytes than did recipients of wild-type bone marrow. The Ly6C
−
monocytes remaining in the bone marrow of
Nr4a1
−/−
mice were arrested in S phase of the cell cycle and underwent apoptosis. Thus, NR4A1 functions as a master regulator of the differentiation and survival of 'patrolling' Ly6C
−
monocytes.</description><identifier>ISSN: 1529-2908</identifier><identifier>EISSN: 1529-2916</identifier><identifier>DOI: 10.1038/ni.2063</identifier><identifier>PMID: 21725321</identifier><language>eng</language><publisher>New York: Nature Publishing Group US</publisher><subject>631/136/142 ; 631/250/2504/342 ; 631/45/612/822 ; Animals ; Antigens, Ly - immunology ; Apoptosis - immunology ; Biomedical and Life Sciences ; Biomedicine ; Bone marrow ; Bone Marrow - immunology ; Cell Cycle - immunology ; Cell Differentiation - immunology ; DNA Damage - immunology ; Flow Cytometry ; Immunology ; Infectious Diseases ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Monocytes - immunology ; Nuclear Receptor Subfamily 4, Group A, Member 1 - genetics ; Nuclear Receptor Subfamily 4, Group A, Member 1 - immunology ; Reverse Transcriptase Polymerase Chain Reaction ; RNA, Messenger - chemistry ; RNA, Messenger - genetics ; Specific Pathogen-Free Organisms</subject><ispartof>Nature immunology, 2011-07, Vol.12 (8), p.778-785</ispartof><rights>Springer Nature America, Inc. 2011</rights><rights>Copyright Nature Publishing Group Aug 2011</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c494t-d77cec5bb3b88aae64883b961a25c75bb8c1a9dd8da4e3afb3e4e1d60a854ff13</citedby><cites>FETCH-LOGICAL-c494t-d77cec5bb3b88aae64883b961a25c75bb8c1a9dd8da4e3afb3e4e1d60a854ff13</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/ni.2063$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1038/ni.2063$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>230,314,776,780,881,27903,27904,41467,42536,51298</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21725321$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Hanna, Richard N</creatorcontrib><creatorcontrib>Carlin, Leo M</creatorcontrib><creatorcontrib>Hubbeling, Harper G</creatorcontrib><creatorcontrib>Nackiewicz, Dominika</creatorcontrib><creatorcontrib>Green, Angela M</creatorcontrib><creatorcontrib>Punt, Jennifer A</creatorcontrib><creatorcontrib>Geissmann, Frederic</creatorcontrib><creatorcontrib>Hedrick, Catherine C</creatorcontrib><title>The transcription factor NR4A1 (Nur77) controls bone marrow differentiation and the survival of Ly6C− monocytes</title><title>Nature immunology</title><addtitle>Nat Immunol</addtitle><addtitle>Nat Immunol</addtitle><description>Ly6C
–
monocytes patrol blood vessels by crawling along uninflamed vasculature. Hedrick and colleagues show that the transcription factor NR4A1 is required for the development and survival of Ly6C
–
monocytes.
The transcription factors that regulate differentiation into the monocyte subset in bone marrow have not yet been identified. Here we found that the orphan nuclear receptor NR4A1 controlled the differentiation of Ly6C
−
monocytes. Ly6C
−
monocytes, which function in a surveillance role in circulation, were absent from
Nr4a1
−/−
mice. Normal numbers of myeloid progenitor cells were present in
Nr4a1
−/−
mice, which indicated that the defect occurred during later stages of monocyte development. The defect was cell intrinsic, as wild-type mice that received bone marrow from
Nr4a1
−/−
mice developed fewer patrolling monocytes than did recipients of wild-type bone marrow. The Ly6C
−
monocytes remaining in the bone marrow of
Nr4a1
−/−
mice were arrested in S phase of the cell cycle and underwent apoptosis. Thus, NR4A1 functions as a master regulator of the differentiation and survival of 'patrolling' Ly6C
−
monocytes.</description><subject>631/136/142</subject><subject>631/250/2504/342</subject><subject>631/45/612/822</subject><subject>Animals</subject><subject>Antigens, Ly - immunology</subject><subject>Apoptosis - immunology</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Bone marrow</subject><subject>Bone Marrow - immunology</subject><subject>Cell Cycle - immunology</subject><subject>Cell Differentiation - immunology</subject><subject>DNA Damage - immunology</subject><subject>Flow Cytometry</subject><subject>Immunology</subject><subject>Infectious Diseases</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Mice, Knockout</subject><subject>Monocytes - immunology</subject><subject>Nuclear Receptor Subfamily 4, Group A, Member 1 - genetics</subject><subject>Nuclear Receptor Subfamily 4, Group A, Member 1 - immunology</subject><subject>Reverse Transcriptase Polymerase Chain Reaction</subject><subject>RNA, Messenger - 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immunology</topic><topic>Apoptosis - immunology</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Bone marrow</topic><topic>Bone Marrow - immunology</topic><topic>Cell Cycle - immunology</topic><topic>Cell Differentiation - immunology</topic><topic>DNA Damage - immunology</topic><topic>Flow Cytometry</topic><topic>Immunology</topic><topic>Infectious Diseases</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Mice, Knockout</topic><topic>Monocytes - immunology</topic><topic>Nuclear Receptor Subfamily 4, Group A, Member 1 - genetics</topic><topic>Nuclear Receptor Subfamily 4, Group A, Member 1 - immunology</topic><topic>Reverse Transcriptase Polymerase Chain Reaction</topic><topic>RNA, Messenger - chemistry</topic><topic>RNA, Messenger - genetics</topic><topic>Specific Pathogen-Free Organisms</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Hanna, Richard N</creatorcontrib><creatorcontrib>Carlin, Leo M</creatorcontrib><creatorcontrib>Hubbeling, Harper G</creatorcontrib><creatorcontrib>Nackiewicz, Dominika</creatorcontrib><creatorcontrib>Green, Angela M</creatorcontrib><creatorcontrib>Punt, Jennifer A</creatorcontrib><creatorcontrib>Geissmann, Frederic</creatorcontrib><creatorcontrib>Hedrick, Catherine C</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Immunology Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Nature immunology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Hanna, Richard N</au><au>Carlin, Leo M</au><au>Hubbeling, Harper G</au><au>Nackiewicz, Dominika</au><au>Green, Angela M</au><au>Punt, Jennifer A</au><au>Geissmann, Frederic</au><au>Hedrick, Catherine C</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The transcription factor NR4A1 (Nur77) controls bone marrow differentiation and the survival of Ly6C− monocytes</atitle><jtitle>Nature immunology</jtitle><stitle>Nat Immunol</stitle><addtitle>Nat Immunol</addtitle><date>2011-07-03</date><risdate>2011</risdate><volume>12</volume><issue>8</issue><spage>778</spage><epage>785</epage><pages>778-785</pages><issn>1529-2908</issn><eissn>1529-2916</eissn><abstract>Ly6C
–
monocytes patrol blood vessels by crawling along uninflamed vasculature. Hedrick and colleagues show that the transcription factor NR4A1 is required for the development and survival of Ly6C
–
monocytes.
The transcription factors that regulate differentiation into the monocyte subset in bone marrow have not yet been identified. Here we found that the orphan nuclear receptor NR4A1 controlled the differentiation of Ly6C
−
monocytes. Ly6C
−
monocytes, which function in a surveillance role in circulation, were absent from
Nr4a1
−/−
mice. Normal numbers of myeloid progenitor cells were present in
Nr4a1
−/−
mice, which indicated that the defect occurred during later stages of monocyte development. The defect was cell intrinsic, as wild-type mice that received bone marrow from
Nr4a1
−/−
mice developed fewer patrolling monocytes than did recipients of wild-type bone marrow. The Ly6C
−
monocytes remaining in the bone marrow of
Nr4a1
−/−
mice were arrested in S phase of the cell cycle and underwent apoptosis. Thus, NR4A1 functions as a master regulator of the differentiation and survival of 'patrolling' Ly6C
−
monocytes.</abstract><cop>New York</cop><pub>Nature Publishing Group US</pub><pmid>21725321</pmid><doi>10.1038/ni.2063</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1529-2908 |
| ispartof | Nature immunology, 2011-07, Vol.12 (8), p.778-785 |
| issn | 1529-2908 1529-2916 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_3324395 |
| source | MEDLINE; Springer Nature - Complete Springer Journals; Nature Journals Online |
| subjects | 631/136/142 631/250/2504/342 631/45/612/822 Animals Antigens, Ly - immunology Apoptosis - immunology Biomedical and Life Sciences Biomedicine Bone marrow Bone Marrow - immunology Cell Cycle - immunology Cell Differentiation - immunology DNA Damage - immunology Flow Cytometry Immunology Infectious Diseases Mice Mice, Inbred C57BL Mice, Knockout Monocytes - immunology Nuclear Receptor Subfamily 4, Group A, Member 1 - genetics Nuclear Receptor Subfamily 4, Group A, Member 1 - immunology Reverse Transcriptase Polymerase Chain Reaction RNA, Messenger - chemistry RNA, Messenger - genetics Specific Pathogen-Free Organisms |
| title | The transcription factor NR4A1 (Nur77) controls bone marrow differentiation and the survival of Ly6C− monocytes |
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