Cytokines regulate postnatal hematopoietic stem cell expansion: opposing roles of thrombopoietin and LNK.
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.
Buza-Vidas
Natalija
N
Hematopoietic Stem Cell Laboratory, Lund Strategic Research Center for Stem Cell Biology and Cell Therapy, Lund University, Sweden.
Antonchuk
Jennifer
J
Qian
Hong
H
Månsson
Robert
R
Luc
Sidinh
S
Zandi
Sasan
S
Anderson
Kristina
K
Takaki
Satoshi
S
Nygren
Jens M
JM
Jensen
Christina T
CT
Jacobsen
Sten Eirik W
SE
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*
D048868:Adaptor Proteins, Signal Transducing; D016207:Cytokines; D047908:Intracellular Signaling Peptides and Proteins; C490777:Lnk protein, mouse; D008565:Membrane Proteins; D011506:Proteins; D013926:Thrombopoietin