Ontology type: schema:ScholarlyArticle
2014-11
AUTHORSMeng Zhao, John M Perry, Heather Marshall, Aparna Venkatraman, Pengxu Qian, Xi C He, Jasimuddin Ahamed, Linheng Li
ABSTRACTMultiple bone marrow stromal cell types have been identified as hematopoietic stem cell (HSC)-regulating niche cells. However, whether HSC progeny can serve directly as HSC niche cells has not previously been shown. Here we report a dichotomous role of megakaryocytes (MKs) in both maintaining HSC quiescence during homeostasis and promoting HSC regeneration after chemotherapeutic stress. We show that MKs are physically associated with HSCs in the bone marrow of mice and that MK ablation led to activation of quiescent HSCs and increased HSC proliferation. RNA sequencing (RNA-seq) analysis revealed that transforming growth factor β1 (encoded by Tgfb1) is expressed at higher levels in MKs as compared to other stromal niche cells. MK ablation led to reduced levels of biologically active TGF-β1 protein in the bone marrow and nuclear-localized phosphorylated SMAD2/3 (pSMAD2/3) in HSCs, suggesting that MKs maintain HSC quiescence through TGF-β-SMAD signaling. Indeed, TGF-β1 injection into mice in which MKs had been ablated restored HSC quiescence, and conditional deletion of Tgfb1 in MKs increased HSC activation and proliferation. These data demonstrate that TGF-β1 is a dominant signal emanating from MKs that maintains HSC quiescence. However, under conditions of chemotherapeutic challenge, MK ablation resulted in a severe defect in HSC expansion. In response to stress, fibroblast growth factor 1 (FGF1) signaling from MKs transiently dominates over TGF-β inhibitory signaling to stimulate HSC expansion. Overall, these observations demonstrate that MKs serve as HSC-derived niche cells to dynamically regulate HSC function. More... »
PAGES1321-1326
http://scigraph.springernature.com/pub.10.1038/nm.3706
DOIhttp://dx.doi.org/10.1038/nm.3706
DIMENSIONShttps://app.dimensions.ai/details/publication/pub.1030879821
PUBMEDhttps://www.ncbi.nlm.nih.gov/pubmed/25326798
JSON-LD is the canonical representation for SciGraph data.
TIP: You can open this SciGraph record using an external JSON-LD service: JSON-LD Playground Google SDTT
[
{
"@context": "https://springernature.github.io/scigraph/jsonld/sgcontext.json",
"about": [
{
"id": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/0601",
"inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/",
"name": "Biochemistry and Cell Biology",
"type": "DefinedTerm"
},
{
"id": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/06",
"inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/",
"name": "Biological Sciences",
"type": "DefinedTerm"
},
{
"inDefinedTermSet": "https://www.nlm.nih.gov/mesh/",
"name": "Animals",
"type": "DefinedTerm"
},
{
"inDefinedTermSet": "https://www.nlm.nih.gov/mesh/",
"name": "Cell Cycle",
"type": "DefinedTerm"
},
{
"inDefinedTermSet": "https://www.nlm.nih.gov/mesh/",
"name": "Cell Proliferation",
"type": "DefinedTerm"
},
{
"inDefinedTermSet": "https://www.nlm.nih.gov/mesh/",
"name": "Fibroblast Growth Factor 1",
"type": "DefinedTerm"
},
{
"inDefinedTermSet": "https://www.nlm.nih.gov/mesh/",
"name": "Fluorouracil",
"type": "DefinedTerm"
},
{
"inDefinedTermSet": "https://www.nlm.nih.gov/mesh/",
"name": "Hematopoietic Stem Cells",
"type": "DefinedTerm"
},
{
"inDefinedTermSet": "https://www.nlm.nih.gov/mesh/",
"name": "Homeostasis",
"type": "DefinedTerm"
},
{
"inDefinedTermSet": "https://www.nlm.nih.gov/mesh/",
"name": "Megakaryocytes",
"type": "DefinedTerm"
},
{
"inDefinedTermSet": "https://www.nlm.nih.gov/mesh/",
"name": "Mice, Inbred C57BL",
"type": "DefinedTerm"
},
{
"inDefinedTermSet": "https://www.nlm.nih.gov/mesh/",
"name": "Regeneration",
"type": "DefinedTerm"
},
{
"inDefinedTermSet": "https://www.nlm.nih.gov/mesh/",
"name": "Sequence Analysis, RNA",
"type": "DefinedTerm"
},
{
"inDefinedTermSet": "https://www.nlm.nih.gov/mesh/",
"name": "Signal Transduction",
"type": "DefinedTerm"
},
{
"inDefinedTermSet": "https://www.nlm.nih.gov/mesh/",
"name": "Stress, Physiological",
"type": "DefinedTerm"
},
{
"inDefinedTermSet": "https://www.nlm.nih.gov/mesh/",
"name": "Transforming Growth Factor beta",
"type": "DefinedTerm"
}
],
"author": [
{
"affiliation": {
"alternateName": "Stowers Institute for Medical Research",
"id": "https://www.grid.ac/institutes/grid.250820.d",
"name": [
"Stowers Institute for Medical Research, Kansas City, Missouri, USA."
],
"type": "Organization"
},
"familyName": "Zhao",
"givenName": "Meng",
"id": "sg:person.0677605223.47",
"sameAs": [
"https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0677605223.47"
],
"type": "Person"
},
{
"affiliation": {
"alternateName": "Stowers Institute for Medical Research",
"id": "https://www.grid.ac/institutes/grid.250820.d",
"name": [
"Stowers Institute for Medical Research, Kansas City, Missouri, USA."
],
"type": "Organization"
},
"familyName": "Perry",
"givenName": "John M",
"id": "sg:person.0615721257.99",
"sameAs": [
"https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0615721257.99"
],
"type": "Person"
},
{
"affiliation": {
"alternateName": "Stowers Institute for Medical Research",
"id": "https://www.grid.ac/institutes/grid.250820.d",
"name": [
"Stowers Institute for Medical Research, Kansas City, Missouri, USA."
],
"type": "Organization"
},
"familyName": "Marshall",
"givenName": "Heather",
"id": "sg:person.0654227662.59",
"sameAs": [
"https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0654227662.59"
],
"type": "Person"
},
{
"affiliation": {
"alternateName": "Christian Medical College & Hospital",
"id": "https://www.grid.ac/institutes/grid.11586.3b",
"name": [
"Stowers Institute for Medical Research, Kansas City, Missouri, USA.",
"Centre for Stem Cell Research, Christian Medical College, Vellore, India."
],
"type": "Organization"
},
"familyName": "Venkatraman",
"givenName": "Aparna",
"id": "sg:person.01360737223.32",
"sameAs": [
"https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01360737223.32"
],
"type": "Person"
},
{
"affiliation": {
"alternateName": "Stowers Institute for Medical Research",
"id": "https://www.grid.ac/institutes/grid.250820.d",
"name": [
"Stowers Institute for Medical Research, Kansas City, Missouri, USA."
],
"type": "Organization"
},
"familyName": "Qian",
"givenName": "Pengxu",
"id": "sg:person.01076413736.11",
"sameAs": [
"https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01076413736.11"
],
"type": "Person"
},
{
"affiliation": {
"alternateName": "Stowers Institute for Medical Research",
"id": "https://www.grid.ac/institutes/grid.250820.d",
"name": [
"Stowers Institute for Medical Research, Kansas City, Missouri, USA."
],
"type": "Organization"
},
"familyName": "He",
"givenName": "Xi C",
"id": "sg:person.0716104267.88",
"sameAs": [
"https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0716104267.88"
],
"type": "Person"
},
{
"affiliation": {
"alternateName": "Rockefeller University",
"id": "https://www.grid.ac/institutes/grid.134907.8",
"name": [
"Laboratory of Blood and Vascular Biology, Rockefeller University, New York, New York, USA."
],
"type": "Organization"
},
"familyName": "Ahamed",
"givenName": "Jasimuddin",
"id": "sg:person.0654512422.84",
"sameAs": [
"https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0654512422.84"
],
"type": "Person"
},
{
"affiliation": {
"alternateName": "University of Kansas Medical Center",
"id": "https://www.grid.ac/institutes/grid.412016.0",
"name": [
"Stowers Institute for Medical Research, Kansas City, Missouri, USA.",
"Department of Pathology and Laboratory Medicine, University of Kansas Medical Center, Kansas City, Kansas, USA."
],
"type": "Organization"
},
"familyName": "Li",
"givenName": "Linheng",
"id": "sg:person.0746360701.12",
"sameAs": [
"https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0746360701.12"
],
"type": "Person"
}
],
"citation": [
{
"id": "sg:pub.10.1038/nm.3364",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1000207099",
"https://doi.org/10.1038/nm.3364"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1182/blood-2012-10-463414",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1001679732"
],
"type": "CreativeWork"
},
{
"id": "sg:pub.10.1038/nature07815",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1002035943",
"https://doi.org/10.1038/nature07815"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1084/jem.20121610",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1003376253"
],
"type": "CreativeWork"
},
{
"id": "sg:pub.10.1038/nature02040",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1003509222",
"https://doi.org/10.1038/nature02040"
],
"type": "CreativeWork"
},
{
"id": "sg:pub.10.1038/nature02040",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1003509222",
"https://doi.org/10.1038/nature02040"
],
"type": "CreativeWork"
},
{
"id": "sg:pub.10.1038/nmeth762",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1004001535",
"https://doi.org/10.1038/nmeth762"
],
"type": "CreativeWork"
},
{
"id": "sg:pub.10.1038/nmeth762",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1004001535",
"https://doi.org/10.1038/nmeth762"
],
"type": "CreativeWork"
},
{
"id": "sg:pub.10.1038/nmeth762",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1004001535",
"https://doi.org/10.1038/nmeth762"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1182/blood-2008-10-183459",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1004940144"
],
"type": "CreativeWork"
},
{
"id": "sg:pub.10.1038/nrc1074",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1012947440",
"https://doi.org/10.1038/nrc1074"
],
"type": "CreativeWork"
},
{
"id": "sg:pub.10.1038/nrc1074",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1012947440",
"https://doi.org/10.1038/nrc1074"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1016/s1534-5807(03)00018-2",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1013030910"
],
"type": "CreativeWork"
},
{
"id": "sg:pub.10.1038/nature10783",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1013056252",
"https://doi.org/10.1038/nature10783"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1182/blood-2008-04-146480",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1013505376"
],
"type": "CreativeWork"
},
{
"id": "sg:pub.10.1038/nm.3707",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1013797677",
"https://doi.org/10.1038/nm.3707"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1182/blood-2011-11-394692",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1014758655"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1002/dvg.20516",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1015757693"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1002/dvg.20516",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1015757693"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1111/j.1365-2141.2006.06215.x",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1016800115"
],
"type": "CreativeWork"
},
{
"id": "sg:pub.10.1038/nature07639",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1018866560",
"https://doi.org/10.1038/nature07639"
],
"type": "CreativeWork"
},
{
"id": "sg:pub.10.1038/nm.3057",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1019946609",
"https://doi.org/10.1038/nm.3057"
],
"type": "CreativeWork"
},
{
"id": "sg:pub.10.1038/nature12612",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1019975723",
"https://doi.org/10.1038/nature12612"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1182/blood-2011-11-393991",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1020786494"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1016/j.cell.2012.05.041",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1021798129"
],
"type": "CreativeWork"
},
{
"id": "sg:pub.10.1038/nn.2467",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1022194277",
"https://doi.org/10.1038/nn.2467"
],
"type": "CreativeWork"
},
{
"id": "sg:pub.10.1038/nn.2467",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1022194277",
"https://doi.org/10.1038/nn.2467"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1096/fj.09-134882",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1022674463"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1073/pnas.202614899",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1022719048"
],
"type": "CreativeWork"
},
{
"id": "sg:pub.10.1038/nature09262",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1022774714",
"https://doi.org/10.1038/nature09262"
],
"type": "CreativeWork"
},
{
"id": "sg:pub.10.1038/nature09262",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1022774714",
"https://doi.org/10.1038/nature09262"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1101/gad.17421911",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1028751150"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1182/blood-2009-11-253534",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1029125218"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1182/blood-2006-04-020362",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1030006582"
],
"type": "CreativeWork"
},
{
"id": "sg:pub.10.1038/nm973",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1030063626",
"https://doi.org/10.1038/nm973"
],
"type": "CreativeWork"
},
{
"id": "sg:pub.10.1038/nm973",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1030063626",
"https://doi.org/10.1038/nm973"
],
"type": "CreativeWork"
},
{
"id": "sg:pub.10.1038/nm1342",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1031150090",
"https://doi.org/10.1038/nm1342"
],
"type": "CreativeWork"
},
{
"id": "sg:pub.10.1038/nm1342",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1031150090",
"https://doi.org/10.1038/nm1342"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1016/j.scr.2013.05.007",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1033091862"
],
"type": "CreativeWork"
},
{
"id": "sg:pub.10.1038/nature02041",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1033616640",
"https://doi.org/10.1038/nature02041"
],
"type": "CreativeWork"
},
{
"id": "sg:pub.10.1038/nature02041",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1033616640",
"https://doi.org/10.1038/nature02041"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1084/jem.20101688",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1037001611"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1182/blood-2011-09-377648",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1037438828"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1182/blood-2004-06-2159",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1038659128"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1371/journal.pone.0051361",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1039779129"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1016/j.cell.2011.09.053",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1042045251"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1126/science.1180794",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1043635280"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1016/j.immuni.2006.10.016",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1044067411"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1016/j.cell.2005.05.026",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1048721879"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1002/gene.10028",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1050349012"
],
"type": "CreativeWork"
}
],
"datePublished": "2014-11",
"datePublishedReg": "2014-11-01",
"description": "Multiple bone marrow stromal cell types have been identified as hematopoietic stem cell (HSC)-regulating niche cells. However, whether HSC progeny can serve directly as HSC niche cells has not previously been shown. Here we report a dichotomous role of megakaryocytes (MKs) in both maintaining HSC quiescence during homeostasis and promoting HSC regeneration after chemotherapeutic stress. We show that MKs are physically associated with HSCs in the bone marrow of mice and that MK ablation led to activation of quiescent HSCs and increased HSC proliferation. RNA sequencing (RNA-seq) analysis revealed that transforming growth factor \u03b21 (encoded by Tgfb1) is expressed at higher levels in MKs as compared to other stromal niche cells. MK ablation led to reduced levels of biologically active TGF-\u03b21 protein in the bone marrow and nuclear-localized phosphorylated SMAD2/3 (pSMAD2/3) in HSCs, suggesting that MKs maintain HSC quiescence through TGF-\u03b2-SMAD signaling. Indeed, TGF-\u03b21 injection into mice in which MKs had been ablated restored HSC quiescence, and conditional deletion of Tgfb1 in MKs increased HSC activation and proliferation. These data demonstrate that TGF-\u03b21 is a dominant signal emanating from MKs that maintains HSC quiescence. However, under conditions of chemotherapeutic challenge, MK ablation resulted in a severe defect in HSC expansion. In response to stress, fibroblast growth factor 1 (FGF1) signaling from MKs transiently dominates over TGF-\u03b2 inhibitory signaling to stimulate HSC expansion. Overall, these observations demonstrate that MKs serve as HSC-derived niche cells to dynamically regulate HSC function. ",
"genre": "research_article",
"id": "sg:pub.10.1038/nm.3706",
"inLanguage": [
"en"
],
"isAccessibleForFree": false,
"isPartOf": [
{
"id": "sg:journal.1113716",
"issn": [
"1078-8956",
"1546-170X"
],
"name": "Nature Medicine",
"type": "Periodical"
},
{
"issueNumber": "11",
"type": "PublicationIssue"
},
{
"type": "PublicationVolume",
"volumeNumber": "20"
}
],
"name": "Megakaryocytes maintain homeostatic quiescence and promote post-injury regeneration of hematopoietic stem cells",
"pagination": "1321-1326",
"productId": [
{
"name": "readcube_id",
"type": "PropertyValue",
"value": [
"931b960845181b36e7ae972f31769b8514aff1c1112cc67ce7915e8dcdaabe62"
]
},
{
"name": "pubmed_id",
"type": "PropertyValue",
"value": [
"25326798"
]
},
{
"name": "nlm_unique_id",
"type": "PropertyValue",
"value": [
"9502015"
]
},
{
"name": "doi",
"type": "PropertyValue",
"value": [
"10.1038/nm.3706"
]
},
{
"name": "dimensions_id",
"type": "PropertyValue",
"value": [
"pub.1030879821"
]
}
],
"sameAs": [
"https://doi.org/10.1038/nm.3706",
"https://app.dimensions.ai/details/publication/pub.1030879821"
],
"sdDataset": "articles",
"sdDatePublished": "2019-04-11T00:04",
"sdLicense": "https://scigraph.springernature.com/explorer/license/",
"sdPublisher": {
"name": "Springer Nature - SN SciGraph project",
"type": "Organization"
},
"sdSource": "s3://com-uberresearch-data-dimensions-target-20181106-alternative/cleanup/v134/2549eaecd7973599484d7c17b260dba0a4ecb94b/merge/v9/a6c9fde33151104705d4d7ff012ea9563521a3ce/jats-lookup/v90/0000000001_0000000264/records_8695_00000425.jsonl",
"type": "ScholarlyArticle",
"url": "http://www.nature.com/articles/nm.3706"
}
]Download the RDF metadata as: json-ld nt turtle xml License info
JSON-LD is a popular format for linked data which is fully compatible with JSON.
curl -H 'Accept: application/ld+json' 'https://scigraph.springernature.com/pub.10.1038/nm.3706'
N-Triples is a line-based linked data format ideal for batch operations.
curl -H 'Accept: application/n-triples' 'https://scigraph.springernature.com/pub.10.1038/nm.3706'
Turtle is a human-readable linked data format.
curl -H 'Accept: text/turtle' 'https://scigraph.springernature.com/pub.10.1038/nm.3706'
RDF/XML is a standard XML format for linked data.
curl -H 'Accept: application/rdf+xml' 'https://scigraph.springernature.com/pub.10.1038/nm.3706'
This table displays all metadata directly associated to this object as RDF triples.
320 TRIPLES
21 PREDICATES
83 URIs
35 LITERALS
23 BLANK NODES