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dc.contributor.authorLu, Jiayun
dc.contributor.authorSun, Yan
dc.contributor.authorNombela-Arrieta, Cesar
dc.contributor.authorDu, Karrie P.
dc.contributor.authorPark, Shin-Young
dc.contributor.authorChai, Li
dc.contributor.authorWalkley, Carl
dc.contributor.authorLuo, Hongbo
dc.contributor.authorSilberstein, Leslie E.
dc.date.accessioned2014-11-05T18:02:41Z
dc.date.issued2012
dc.identifier.citationLu, Jiayun, Yan Sun, Cesar Nombela-Arrieta, Karrie P. Du, Shin-Young Park, Li Chai, Carl Walkley, Hongbo R. Luo, and Leslie E. Silberstein. 2012. “Fak Depletion in Both Hematopoietic and Nonhematopoietic Niche Cells Leads to Hematopoietic Stem Cell Expansion.” Experimental Hematology 40 (4) (April): 307–317.e3. doi:10.1016/j.exphem.2011.11.010. http://dx.doi.org/10.1016/j.exphem.2011.11.010.en_US
dc.identifier.issn0301-472Xen_US
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:13350201
dc.description.abstractHematopoietic stem cells (HSCs) reside in complex bone marrow microenvironments, where niche-induced signals regulate hematopoiesis. Focal adhesion kinase (Fak) is a nonreceptor protein tyrosine kinase that plays an essential role in many cell types, where its activation controls adhesion, motility, and survival. Fak expression is relatively increased in HSCs compared to progenitors and mature blood cells. Therefore, we explored its role in HSC homeostasis. We have used the Mx1-CreLinducible conditional knockout mouse model to investigate the effects of Fak deletion in bone marrow compartments. The total number as well as the fraction of cycling \(Lin^-Sca-1^+c-kit^+\) (LSK) cells is increased in \(Fak^{-/-}\) mice compared to controls, while hematopoietic progenitors and mature blood cells are unaffected. Bone marrow cells from \(Fak^{-/-}\) mice exhibit enhanced, long-term (i.e., 20-week duration) engraftment in competitive transplantation assays. Intrinsic Fak function was assessed in serial transplantation assays, which showed that HSCs (\(Lin^-Sca-1^+c-kit^+CD34^-Flk-2^-\) cells) sorted from \(Fak^{-/-}\) mice have similar self-renewal and engraftment ability on a per-cell basis as wild-type HSCs. When Fak deletion is induced after engraftment of \(Fak^{fl/fl}Mx1-Cre^+\) bone marrow cells into wild-type recipient mice, the number of LSKs is unchanged. In conclusion, Fak inactivation does not intrinsically regulate HSC behavior and is not essential for steady- state hematopoiesis. However, widespread Fak inactivation in the hematopoietic system induces an increased and activated HSC pool size, potentially as a result of altered reciprocal interactions between HSCs and their microenvironment.en_US
dc.language.isoen_USen_US
dc.publisherElsevier BVen_US
dc.relation.isversionofdoi:10.1016/j.exphem.2011.11.010en_US
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pubmed/22155722en_US
dash.licenseMETA_ONLY
dc.titleFak Depletion in Both Hematopoietic and Nonhematopoietic Niche Cells Leads to Hematopoietic Stem Cell Expansionen_US
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden_US
dc.relation.journalExperimental Hematologyen_US
dash.depositing.authorLuo, Hongbo
dash.embargo.until10000-01-01
dc.identifier.doi10.1016/j.exphem.2011.11.010*
dash.contributor.affiliatedSilberstein, Leslie
dash.contributor.affiliatedChai, Li
dash.contributor.affiliatedSun, Yan
dash.contributor.affiliatedLuo, Hongbo
dash.contributor.affiliatedPark, Shin-Young


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