Show simple item record

dc.contributor.authorNakagawa, M.M.
dc.contributor.authorDavis, H.
dc.contributor.authorRathinam, C.V.
dc.date.accessioned2019-04-05T13:55:13Z
dc.date.available2019-04-05T13:55:13Z
dc.date.issued2018
dc.identifier.urihttps://www.scopus.com/inward/record.uri?eid=2-s2.0-85056601601&doi=10.1016%2fj.scr.2018.10.020&partnerID=40&md5=95811b47849374e41ed4c272bb0c4248
dc.identifier.urihttp://hdl.handle.net/10713/8829
dc.description.abstractInflammatory signals have been shown to play a critical role in controlling the maintenance and functions of hematopoietic stem cells (HSCs). While the significance of inflammation in hematopoiesis has begun to unfold, molecular mechanisms and players that govern this mode of HSC regulation remain largely unknown. The E3 ubiquitin ligase A20 has been considered as a central gatekeeper of inflammation. Here, we have specifically depleted A20 in multi-potent progenitors (MPPs) and studied its impact on hematopoiesis. Our data suggest that lack of A20 in Flt3 + progenitors causes modest alterations in hematopoietic differentiation. Analysis of hematopoietic stem and progenitor cell (HSPC) pool revealed alterations in HSPC subsets including, HSCs, MPP1, MPP2, MPP3 and MPP4. Interestingly, A20 deficiency in MPPs caused loss of HSC quiescence and compromised long-term hematopoietic reconstitution. Mechanistic studies identified that A20 deficiency caused elevated levels of Interferon-? signaling and downregulation of p57 in HSCs. In essence, these studies identified A20 as a key regulator of HSC quiescence and cell fate decisions. © 2018en_US
dc.description.sponsorshipWe thank Drs. Bleul and Boehm for providing the Flt3-Cre mice. This work was supported by grants from the NHLBI HL132194 (CVR).en_US
dc.description.urihttps://dx.doi.org/10.1016/j.scr.2018.10.020en_US
dc.language.isoEnglishen_US
dc.publisherElsevier B.V.en_US
dc.relation.ispartofStem Cell Research
dc.subject.meshHematopoietic Stem Cellsen_US
dc.subject.meshUbiquitin-Protein Ligases--deficiencyen_US
dc.titleA20 deficiency in multipotent progenitors perturbs quiescence of hematopoietic stem cellsen_US
dc.typeArticleen_US
dc.identifier.doi10.1016/j.scr.2018.10.020
dc.identifier.pmid30445411


Files in this item

Thumbnail
Name:
Publisher version

This item appears in the following Collection(s)

Show simple item record