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Cytokines regulate postnatal hematopoietic stem cell expansion: Opposing roles of thrombopoietin and LNK
Hematopoietic Stem Cell Laboratory, Lund Strategic Research Center for Stem Cell Biology and Cell Therapy, Lund University, Sweden.
Hematopoietic Stem Cell Laboratory, Lund Strategic Research Center for Stem Cell Biology and Cell Therapy, Lund University, Sweden.
Hematopoietic Stem Cell Laboratory, Lund Strategic Research Center for Stem Cell Biology and Cell Therapy, Lund University, Sweden.
Hematopoietic Stem Cell Laboratory, Lund Strategic Research Center for Stem Cell Biology and Cell Therapy, Lund University, Sweden.
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2006 (English)In: Genes & Development, ISSN 0890-9369, E-ISSN 1549-5477, Vol. 20, no 15, 2018-2023 p.Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
Woodbury, NY, USA: Cold Spring Harbor Laboratory Press (CSHL), 2006. Vol. 20, no 15, 2018-2023 p.
Keyword [en]
Hematopoiesis, LNK, Self-renewal, Stem cells, Thrombopoietin
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:hh:diva-15175DOI: 10.1101/gad.385606ISI: 000239504500007PubMedID: 16882979ScopusID: 2-s2.0-33746591727OAI: oai:DiVA.org:hh-15175DiVA: diva2:419613
Available from: 2011-05-27 Created: 2011-05-27 Last updated: 2015-09-21Bibliographically approved

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Nygren, Jens Martin
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