The MTOR signaling pathway regulates macrophage differentiation from mouse myeloid progenitors by inhibiting autophagy
Understanding of the mechanism for myeloid differentiation provides important insights into the hematopoietic developmental processes. By using an ESC-derived myeloid progenitor cell model, we found that CSF2/GM-CSF triggered macrophage differentiation and activation of the MTOR signaling pathway. A...
Gespeichert in:
Veröffentlicht in: | Autophagy 2019-07, Vol.15 (7), p.1150-1162 |
---|---|
Hauptverfasser: | , , , , , , , , , , , , |
Format: | Artikel |
Sprache: | eng |
Schlagworte: | |
Online-Zugang: | Volltext |
Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
container_end_page | 1162 |
---|---|
container_issue | 7 |
container_start_page | 1150 |
container_title | Autophagy |
container_volume | 15 |
creator | Zhang, Meichao Liu, Furao Zhou, Pingting Wang, Qian Xu, Ci Li, Yanyan Bian, Lei Liu, Yuanhua Zhou, Jiaxi Wang, Fei Yao, Yuan Fang, Yong Li, Dong |
description | Understanding of the mechanism for myeloid differentiation provides important insights into the hematopoietic developmental processes. By using an ESC-derived myeloid progenitor cell model, we found that CSF2/GM-CSF triggered macrophage differentiation and activation of the MTOR signaling pathway. Activation or inhibition of the MTOR signaling enhanced or attenuated macrophage differentiation, respectively, suggesting a critical function. We further showed that macroautophagy/autophagy was inhibited with the addition of CSF2. Furthermore, pharmacological inhibition and genetic modification of autophagy enhanced macrophage differentiation and rescued the inhibitory effect on differentiation caused by MTOR inhibition. Thus, the MTOR signaling pathway regulates macrophage differentiation of myeloid progenitors by inhibiting autophagy. Our results provide new insights into the mechanisms for myeloid differentiation and may prove useful for therapeutic applications of hematopoietic and myeloid progenitor cells.
Abbreviations: 2-DG: 2-deoxy-D-glucose; ADGRE1/F4/80: adhesion G protein-coupled receptor E1; BM: bone marrow; CQ: chloroquine; ECAR: extracellular acidification rate; ESC: embryonic stem cell; CSF2/GM-CSF: colony stimulating factor 2; CSF3/G-CSF: colony stimulating factor 3; HPC: hematopoietic progenitor cell; ITGAM/CD11b: integrin alpha M; LPS: lipopolysaccharide; MFI: median fluorescence intensity; MTOR: mechanistic target of rapamycin kinase; RPS6KB1/p70S6K1: ribosomal protein S6 kinase, polypeptide 1; shRNA: short hairpin RNA; SQSTM1/p62: sequestosome 1. |
doi_str_mv | 10.1080/15548627.2019.1578040 |
format | Article |
fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_6613836</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2186615544</sourcerecordid><originalsourceid>FETCH-LOGICAL-c468t-4a3b95f02ac662e946540936549d7d69c6e5399a1ac890e02b15cd2036be35ef3</originalsourceid><addsrcrecordid>eNp9kctu1DAUhiMEoqXwCCAv2czgS-zEGwSqykUqqoSGtXWSnCRGiR1sT6u8PR5mOoING9s6_s93Ln9RvGZ0y2hN3zEpy1rxassp01smq5qW9ElxeYhvaiXk0_ObVxfFixh_UipUrfnz4kLQipdK08vifjci-ba7-06iHRxM1g1kgTQ-wEoCDvsJEkYyQxv8MsKApLN9jwFdspCsd6QPfiaz30ck84qTtx1Zgh_Q2eRDJM1KrBttY9OBDPv0B7O-LJ71MEV8dbqvih-fbnbXXza3d5-_Xn-83bSlqtOmBNFo2VMOrVIcdalkSbXIp-6qTulWoRRaA4O21hQpb5hsO57nbFBI7MVV8f7IXfbNjF2b-w4wmSXYGcJqPFjz74-zoxn8vVGKiVqoDHh7AgT_a48xmdnGFqcJHOahDWd1luY9l1kqj9K8qxgD9ucyjJqDZ-bRM3PwzJw8y3lv_u7xnPVoUhZ8OAqs632Y4cGHqTMJ1smHPoBrbTTi_zV-A7Bhqaw</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2186615544</pqid></control><display><type>article</type><title>The MTOR signaling pathway regulates macrophage differentiation from mouse myeloid progenitors by inhibiting autophagy</title><source>PubMed Central Free</source><source>EZB-FREE-00999 freely available EZB journals</source><creator>Zhang, Meichao ; Liu, Furao ; Zhou, Pingting ; Wang, Qian ; Xu, Ci ; Li, Yanyan ; Bian, Lei ; Liu, Yuanhua ; Zhou, Jiaxi ; Wang, Fei ; Yao, Yuan ; Fang, Yong ; Li, Dong</creator><creatorcontrib>Zhang, Meichao ; Liu, Furao ; Zhou, Pingting ; Wang, Qian ; Xu, Ci ; Li, Yanyan ; Bian, Lei ; Liu, Yuanhua ; Zhou, Jiaxi ; Wang, Fei ; Yao, Yuan ; Fang, Yong ; Li, Dong</creatorcontrib><description>Understanding of the mechanism for myeloid differentiation provides important insights into the hematopoietic developmental processes. By using an ESC-derived myeloid progenitor cell model, we found that CSF2/GM-CSF triggered macrophage differentiation and activation of the MTOR signaling pathway. Activation or inhibition of the MTOR signaling enhanced or attenuated macrophage differentiation, respectively, suggesting a critical function. We further showed that macroautophagy/autophagy was inhibited with the addition of CSF2. Furthermore, pharmacological inhibition and genetic modification of autophagy enhanced macrophage differentiation and rescued the inhibitory effect on differentiation caused by MTOR inhibition. Thus, the MTOR signaling pathway regulates macrophage differentiation of myeloid progenitors by inhibiting autophagy. Our results provide new insights into the mechanisms for myeloid differentiation and may prove useful for therapeutic applications of hematopoietic and myeloid progenitor cells.
Abbreviations: 2-DG: 2-deoxy-D-glucose; ADGRE1/F4/80: adhesion G protein-coupled receptor E1; BM: bone marrow; CQ: chloroquine; ECAR: extracellular acidification rate; ESC: embryonic stem cell; CSF2/GM-CSF: colony stimulating factor 2; CSF3/G-CSF: colony stimulating factor 3; HPC: hematopoietic progenitor cell; ITGAM/CD11b: integrin alpha M; LPS: lipopolysaccharide; MFI: median fluorescence intensity; MTOR: mechanistic target of rapamycin kinase; RPS6KB1/p70S6K1: ribosomal protein S6 kinase, polypeptide 1; shRNA: short hairpin RNA; SQSTM1/p62: sequestosome 1.</description><identifier>ISSN: 1554-8627</identifier><identifier>EISSN: 1554-8635</identifier><identifier>DOI: 10.1080/15548627.2019.1578040</identifier><identifier>PMID: 30724690</identifier><language>eng</language><publisher>United States: Taylor & Francis</publisher><subject>Autophagy ; CSF2 ; MTOR ; myeloid differentiation ; myeloid progenitors ; Research Paper - Basic Science</subject><ispartof>Autophagy, 2019-07, Vol.15 (7), p.1150-1162</ispartof><rights>2019 Informa UK Limited, trading as Taylor & Francis Group 2019</rights><rights>2019 Informa UK Limited, trading as Taylor & Francis Group 2019 Informa UK Limited, trading as Taylor & Francis Group</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c468t-4a3b95f02ac662e946540936549d7d69c6e5399a1ac890e02b15cd2036be35ef3</citedby><cites>FETCH-LOGICAL-c468t-4a3b95f02ac662e946540936549d7d69c6e5399a1ac890e02b15cd2036be35ef3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6613836/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6613836/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,727,780,784,885,27924,27925,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30724690$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Zhang, Meichao</creatorcontrib><creatorcontrib>Liu, Furao</creatorcontrib><creatorcontrib>Zhou, Pingting</creatorcontrib><creatorcontrib>Wang, Qian</creatorcontrib><creatorcontrib>Xu, Ci</creatorcontrib><creatorcontrib>Li, Yanyan</creatorcontrib><creatorcontrib>Bian, Lei</creatorcontrib><creatorcontrib>Liu, Yuanhua</creatorcontrib><creatorcontrib>Zhou, Jiaxi</creatorcontrib><creatorcontrib>Wang, Fei</creatorcontrib><creatorcontrib>Yao, Yuan</creatorcontrib><creatorcontrib>Fang, Yong</creatorcontrib><creatorcontrib>Li, Dong</creatorcontrib><title>The MTOR signaling pathway regulates macrophage differentiation from mouse myeloid progenitors by inhibiting autophagy</title><title>Autophagy</title><addtitle>Autophagy</addtitle><description>Understanding of the mechanism for myeloid differentiation provides important insights into the hematopoietic developmental processes. By using an ESC-derived myeloid progenitor cell model, we found that CSF2/GM-CSF triggered macrophage differentiation and activation of the MTOR signaling pathway. Activation or inhibition of the MTOR signaling enhanced or attenuated macrophage differentiation, respectively, suggesting a critical function. We further showed that macroautophagy/autophagy was inhibited with the addition of CSF2. Furthermore, pharmacological inhibition and genetic modification of autophagy enhanced macrophage differentiation and rescued the inhibitory effect on differentiation caused by MTOR inhibition. Thus, the MTOR signaling pathway regulates macrophage differentiation of myeloid progenitors by inhibiting autophagy. Our results provide new insights into the mechanisms for myeloid differentiation and may prove useful for therapeutic applications of hematopoietic and myeloid progenitor cells.
Abbreviations: 2-DG: 2-deoxy-D-glucose; ADGRE1/F4/80: adhesion G protein-coupled receptor E1; BM: bone marrow; CQ: chloroquine; ECAR: extracellular acidification rate; ESC: embryonic stem cell; CSF2/GM-CSF: colony stimulating factor 2; CSF3/G-CSF: colony stimulating factor 3; HPC: hematopoietic progenitor cell; ITGAM/CD11b: integrin alpha M; LPS: lipopolysaccharide; MFI: median fluorescence intensity; MTOR: mechanistic target of rapamycin kinase; RPS6KB1/p70S6K1: ribosomal protein S6 kinase, polypeptide 1; shRNA: short hairpin RNA; SQSTM1/p62: sequestosome 1.</description><subject>Autophagy</subject><subject>CSF2</subject><subject>MTOR</subject><subject>myeloid differentiation</subject><subject>myeloid progenitors</subject><subject>Research Paper - Basic Science</subject><issn>1554-8627</issn><issn>1554-8635</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><recordid>eNp9kctu1DAUhiMEoqXwCCAv2czgS-zEGwSqykUqqoSGtXWSnCRGiR1sT6u8PR5mOoING9s6_s93Ln9RvGZ0y2hN3zEpy1rxassp01smq5qW9ElxeYhvaiXk0_ObVxfFixh_UipUrfnz4kLQipdK08vifjci-ba7-06iHRxM1g1kgTQ-wEoCDvsJEkYyQxv8MsKApLN9jwFdspCsd6QPfiaz30ck84qTtx1Zgh_Q2eRDJM1KrBttY9OBDPv0B7O-LJ71MEV8dbqvih-fbnbXXza3d5-_Xn-83bSlqtOmBNFo2VMOrVIcdalkSbXIp-6qTulWoRRaA4O21hQpb5hsO57nbFBI7MVV8f7IXfbNjF2b-w4wmSXYGcJqPFjz74-zoxn8vVGKiVqoDHh7AgT_a48xmdnGFqcJHOahDWd1luY9l1kqj9K8qxgD9ucyjJqDZ-bRM3PwzJw8y3lv_u7xnPVoUhZ8OAqs632Y4cGHqTMJ1smHPoBrbTTi_zV-A7Bhqaw</recordid><startdate>20190703</startdate><enddate>20190703</enddate><creator>Zhang, Meichao</creator><creator>Liu, Furao</creator><creator>Zhou, Pingting</creator><creator>Wang, Qian</creator><creator>Xu, Ci</creator><creator>Li, Yanyan</creator><creator>Bian, Lei</creator><creator>Liu, Yuanhua</creator><creator>Zhou, Jiaxi</creator><creator>Wang, Fei</creator><creator>Yao, Yuan</creator><creator>Fang, Yong</creator><creator>Li, Dong</creator><general>Taylor & Francis</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20190703</creationdate><title>The MTOR signaling pathway regulates macrophage differentiation from mouse myeloid progenitors by inhibiting autophagy</title><author>Zhang, Meichao ; Liu, Furao ; Zhou, Pingting ; Wang, Qian ; Xu, Ci ; Li, Yanyan ; Bian, Lei ; Liu, Yuanhua ; Zhou, Jiaxi ; Wang, Fei ; Yao, Yuan ; Fang, Yong ; Li, Dong</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c468t-4a3b95f02ac662e946540936549d7d69c6e5399a1ac890e02b15cd2036be35ef3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Autophagy</topic><topic>CSF2</topic><topic>MTOR</topic><topic>myeloid differentiation</topic><topic>myeloid progenitors</topic><topic>Research Paper - Basic Science</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Zhang, Meichao</creatorcontrib><creatorcontrib>Liu, Furao</creatorcontrib><creatorcontrib>Zhou, Pingting</creatorcontrib><creatorcontrib>Wang, Qian</creatorcontrib><creatorcontrib>Xu, Ci</creatorcontrib><creatorcontrib>Li, Yanyan</creatorcontrib><creatorcontrib>Bian, Lei</creatorcontrib><creatorcontrib>Liu, Yuanhua</creatorcontrib><creatorcontrib>Zhou, Jiaxi</creatorcontrib><creatorcontrib>Wang, Fei</creatorcontrib><creatorcontrib>Yao, Yuan</creatorcontrib><creatorcontrib>Fang, Yong</creatorcontrib><creatorcontrib>Li, Dong</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Autophagy</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zhang, Meichao</au><au>Liu, Furao</au><au>Zhou, Pingting</au><au>Wang, Qian</au><au>Xu, Ci</au><au>Li, Yanyan</au><au>Bian, Lei</au><au>Liu, Yuanhua</au><au>Zhou, Jiaxi</au><au>Wang, Fei</au><au>Yao, Yuan</au><au>Fang, Yong</au><au>Li, Dong</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The MTOR signaling pathway regulates macrophage differentiation from mouse myeloid progenitors by inhibiting autophagy</atitle><jtitle>Autophagy</jtitle><addtitle>Autophagy</addtitle><date>2019-07-03</date><risdate>2019</risdate><volume>15</volume><issue>7</issue><spage>1150</spage><epage>1162</epage><pages>1150-1162</pages><issn>1554-8627</issn><eissn>1554-8635</eissn><abstract>Understanding of the mechanism for myeloid differentiation provides important insights into the hematopoietic developmental processes. By using an ESC-derived myeloid progenitor cell model, we found that CSF2/GM-CSF triggered macrophage differentiation and activation of the MTOR signaling pathway. Activation or inhibition of the MTOR signaling enhanced or attenuated macrophage differentiation, respectively, suggesting a critical function. We further showed that macroautophagy/autophagy was inhibited with the addition of CSF2. Furthermore, pharmacological inhibition and genetic modification of autophagy enhanced macrophage differentiation and rescued the inhibitory effect on differentiation caused by MTOR inhibition. Thus, the MTOR signaling pathway regulates macrophage differentiation of myeloid progenitors by inhibiting autophagy. Our results provide new insights into the mechanisms for myeloid differentiation and may prove useful for therapeutic applications of hematopoietic and myeloid progenitor cells.
Abbreviations: 2-DG: 2-deoxy-D-glucose; ADGRE1/F4/80: adhesion G protein-coupled receptor E1; BM: bone marrow; CQ: chloroquine; ECAR: extracellular acidification rate; ESC: embryonic stem cell; CSF2/GM-CSF: colony stimulating factor 2; CSF3/G-CSF: colony stimulating factor 3; HPC: hematopoietic progenitor cell; ITGAM/CD11b: integrin alpha M; LPS: lipopolysaccharide; MFI: median fluorescence intensity; MTOR: mechanistic target of rapamycin kinase; RPS6KB1/p70S6K1: ribosomal protein S6 kinase, polypeptide 1; shRNA: short hairpin RNA; SQSTM1/p62: sequestosome 1.</abstract><cop>United States</cop><pub>Taylor & Francis</pub><pmid>30724690</pmid><doi>10.1080/15548627.2019.1578040</doi><tpages>13</tpages><oa>free_for_read</oa></addata></record> |
fulltext | fulltext |
identifier | ISSN: 1554-8627 |
ispartof | Autophagy, 2019-07, Vol.15 (7), p.1150-1162 |
issn | 1554-8627 1554-8635 |
language | eng |
recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_6613836 |
source | PubMed Central Free; EZB-FREE-00999 freely available EZB journals |
subjects | Autophagy CSF2 MTOR myeloid differentiation myeloid progenitors Research Paper - Basic Science |
title | The MTOR signaling pathway regulates macrophage differentiation from mouse myeloid progenitors by inhibiting autophagy |
url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-25T11%3A30%3A10IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=The%20MTOR%20signaling%20pathway%20regulates%20macrophage%20differentiation%20from%20mouse%20myeloid%20progenitors%20by%20inhibiting%20autophagy&rft.jtitle=Autophagy&rft.au=Zhang,%20Meichao&rft.date=2019-07-03&rft.volume=15&rft.issue=7&rft.spage=1150&rft.epage=1162&rft.pages=1150-1162&rft.issn=1554-8627&rft.eissn=1554-8635&rft_id=info:doi/10.1080/15548627.2019.1578040&rft_dat=%3Cproquest_pubme%3E2186615544%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2186615544&rft_id=info:pmid/30724690&rfr_iscdi=true |