English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Zendy Plus

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Zendy Tools

Zendy Open

The genes and pathways that govern the functions and expansion of hematopoietic stem cells (HSC) are not completely understood. In this study, we investigated the roles of serine/threonine Pim kinases in hematopoiesis in mice. We generated PIM1 transgenic mice (Pim1‐Tx) overexpressing human  PIM1  driven by  vav  hematopoietic promoter/regulatory elements. Compared to wild‐type littermates, Pim1‐Tx mice showed enhanced hematopoiesis as demonstrated by increased numbers of Lin − Sca‐1  + c‐Kit  +  (LSK) hematopoietic stem/progenitor cells and cobblestone area forming cells, higher BrdU incorporation in long‐term HSC population, and a better ability to reconstitute lethally irradiated mice. We then extended our study using  Pim1  −/− ,  Pim2  −/− ,  Pim3  −/−  single knockout (KO) mice. HSCs from  Pim1  −/−  KO mice showed impaired long‐term hematopoietic repopulating capacity in secondary and competitive transplantations. Interestingly, these defects were not observed in HSCs from  Pim2  −/−  or  Pim3  −/−  KO mice. Limiting dilution competitive transplantation assay estimated that the frequency of LSKCD34 −  HSCs was reduced by approximately 28‐fold in  Pim1  −/−  KO mice compared to wild‐type littermates. Mechanistic studies demonstrated an important role of Pim1 kinase in regulating HSC cell proliferation and survival. Finally, our polymerase chain reaction (PCR) array and confirmatory real‐time PCR (RT‐PCR) studies identified several genes including Lef‐1, Pax5, and Gata1 in HSCs that were affected by Pim1 deletion. Our data provide the first direct evidence for the important role of Pim1 kinase in the regulation of HSCs. Our study also dissects out the relative role of individual Pim kinase in HSC functions and regulation. S TEM  C ells   2013;31:1202–1212

Pim1 Serine/Threonine Kinase Regulates the Number and Functions of Murine Hematopoietic Stem Cells