title: Cytokines regulate postnatal hematopoietic stem cell expansion: opposing roles of thrombopoietin and LNK.
abstract: The role of cytokines as regulators of hematopoietic stem cell (HSC) expansion remains elusive. Herein, we identify thrombopoietin (THPO) and the cytokine signaling inhibitor LNK, as opposing physiological regulators of HSC expansion. Lnk(-/-) HSCs continue to expand postnatally, up to 24-fold above normal by 6 mo of age. Within the stem cell compartment, this expansion is highly selective for self-renewing long-term HSCs (LT-HSCs), which show enhanced THPO responsiveness. Lnk(-/-) HSC expansion is dependent on THPO, and 12-wk-old Lnk(-/-)Thpo(-/-) mice have 65-fold fewer LT-HSCs than Lnk(-/-) mice. Expansions of multiple myeloid, but not lymphoid, progenitors in Lnk(-/-) mice also proved THPO-dependent.
authors.affiliation: Hematopoietic Stem Cell Laboratory, Lund Strategic Research Center for Stem Cell Biology and Cell Therapy, Lund University, Sweden.
authors.forename: Natalija
authors.initials: N
authors.lastname: Buza-Vidas
authors.forename: Jennifer
authors.initials: J
authors.lastname: Antonchuk
authors.forename: Hong
authors.initials: H
authors.lastname: Qian
authors.forename: Robert
authors.initials: R
authors.lastname: Månsson
authors.forename: Sidinh
authors.initials: S
authors.lastname: Luc
authors.forename: Sasan
authors.initials: S
authors.lastname: Zandi
authors.forename: Kristina
authors.initials: K
authors.lastname: Anderson
authors.forename: Satoshi
authors.initials: S
authors.lastname: Takaki
authors.forename: Jens M
authors.initials: JM
authors.lastname: Nygren
authors.forename: Christina T
authors.initials: CT
authors.lastname: Jensen
authors.forename: Sten Eirik W
authors.initials: SE
authors.lastname: Jacobsen
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D003114:Colony-Forming Units Assay; D016207:Cytokines / Q000494:pharmacology*; D005260:Female; D018507:Gene Expression Regulation, Developmental; D006410:Hematopoiesis; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins; D008214:Lymphocytes / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D022423:Myeloid Cells / Q000187:drug effects / Q000378:metabolism; D011506:Proteins / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction; D013234:Stem Cells / Q000187:drug effects / Q000378:metabolism; D013926:Thrombopoietin / Q000494:pharmacology*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D016207:Cytokines; D047908:Intracellular Signaling Peptides and Proteins; C490777:Lnk protein, mouse; D008565:Membrane Proteins; D011506:Proteins; D013926:Thrombopoietin