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dc.contributor.authorPoulos, Michael G.
dc.contributor.authorRamalingam, Pradeep
dc.contributor.authorGutkin, Michael C.
dc.contributor.authorKleppe, Maria
dc.contributor.authorGinsberg, Michael
dc.contributor.authorCrowley, Michael J. P.
dc.contributor.authorElemento, Olivier
dc.contributor.authorLevine, Ross L.
dc.contributor.authorRafii, Shahin
dc.contributor.authorKitajewski, Jan
dc.contributor.authorGreenblatt, Matthew B.
dc.contributor.authorShim, Jae-Hyuck
dc.contributor.authorButler, Jason M.
dc.date2022-08-11T08:09:46.000
dc.date.accessioned2022-08-23T16:43:06Z
dc.date.available2022-08-23T16:43:06Z
dc.date.issued2016-12-21
dc.date.submitted2017-05-16
dc.identifier.citationNat Commun. 2016 Dec 21;7:13829. doi: 10.1038/ncomms13829. <a href="https://doi.org/10.1038/ncomms13829">Link to article on publisher's site</a>
dc.identifier.issn2041-1723 (Linking)
dc.identifier.doi10.1038/ncomms13829
dc.identifier.pmid28000664
dc.identifier.urihttp://hdl.handle.net/20.500.14038/40222
dc.description.abstractHaematopoietic stem cells (HSCs) reside in distinct niches within the bone marrow (BM) microenvironment, comprised of endothelial cells (ECs) and tightly associated perivascular constituents that regulate haematopoiesis through the expression of paracrine factors. Here we report that the canonical NF-kappaB pathway in the BM vascular niche is a critical signalling axis that regulates HSC function at steady state and following myelosuppressive insult, in which inhibition of EC NF-kappaB promotes improved HSC function and pan-haematopoietic recovery. Mice expressing an endothelial-specific dominant negative IkappaBalpha cassette under the Tie2 promoter display a marked increase in HSC activity and self-renewal, while promoting the accelerated recovery of haematopoiesis following myelosuppression, in part through protection of the BM microenvironment following radiation and chemotherapeutic-induced insult. Moreover, transplantation of NF-kappaB-inhibited BM ECs enhanced haematopoietic recovery and protected mice from pancytopenia-induced death. These findings pave the way for development of niche-specific cellular approaches for the treatment of haematological disorders requiring myelosuppressive regimens.
dc.language.isoen_US
dc.relation<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=28000664&dopt=Abstract">Link to Article in PubMed</a>
dc.rightsCopyright © 2016, The Author(s).
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectHaematopoietic stem cells
dc.subjectStem-cell niche
dc.subjectCell Biology
dc.subjectDevelopmental Biology
dc.titleEndothelial-specific inhibition of NF-kappaB enhances functional haematopoiesis
dc.typeJournal Article
dc.source.journaltitleNature communications
dc.source.volume7
dc.identifier.legacyfulltexthttps://escholarship.umassmed.edu/cgi/viewcontent.cgi?article=4021&amp;context=oapubs&amp;unstamped=1
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/oapubs/3016
dc.identifier.contextkey10171422
refterms.dateFOA2022-08-23T16:43:06Z
html.description.abstract<p>Haematopoietic stem cells (HSCs) reside in distinct niches within the bone marrow (BM) microenvironment, comprised of endothelial cells (ECs) and tightly associated perivascular constituents that regulate haematopoiesis through the expression of paracrine factors. Here we report that the canonical NF-kappaB pathway in the BM vascular niche is a critical signalling axis that regulates HSC function at steady state and following myelosuppressive insult, in which inhibition of EC NF-kappaB promotes improved HSC function and pan-haematopoietic recovery. Mice expressing an endothelial-specific dominant negative IkappaBalpha cassette under the Tie2 promoter display a marked increase in HSC activity and self-renewal, while promoting the accelerated recovery of haematopoiesis following myelosuppression, in part through protection of the BM microenvironment following radiation and chemotherapeutic-induced insult. Moreover, transplantation of NF-kappaB-inhibited BM ECs enhanced haematopoietic recovery and protected mice from pancytopenia-induced death. These findings pave the way for development of niche-specific cellular approaches for the treatment of haematological disorders requiring myelosuppressive regimens.</p>
dc.identifier.submissionpathoapubs/3016
dc.contributor.departmentDepartment of Medicine, Division of Rheumatology
dc.source.pages13829


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