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

Publication ,  Journal Article
An, N; Lin, Y-W; Mahajan, S; Kellner, JN; Wang, Y; Li, Z; Kraft, AS; Kang, Y
Published in: Stem Cells
June 1, 2013

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.

Duke Scholars

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Published In

Stem Cells

DOI

EISSN

1549-4918

ISSN

1066-5099

Publication Date

June 1, 2013

Volume

31

Issue

6

Start / End Page

1202 / 1212

Publisher

Oxford University Press (OUP)

Related Subject Headings

  • Immunology
  • 32 Biomedical and clinical sciences
  • 31 Biological sciences
  • 11 Medical and Health Sciences
  • 10 Technology
  • 06 Biological Sciences
 

Citation

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An, N., Lin, Y.-W., Mahajan, S., Kellner, J. N., Wang, Y., Li, Z., … Kang, Y. (2013). Pim1 Serine/Threonine Kinase Regulates the Number and Functions of Murine Hematopoietic Stem Cells. Stem Cells, 31(6), 1202–1212. https://doi.org/10.1002/stem.1369
An, Ningfei, Ying-Wei Lin, Sandeep Mahajan, Joshua N. Kellner, Yong Wang, Zihai Li, Andrew S. Kraft, and Yubin Kang. “Pim1 Serine/Threonine Kinase Regulates the Number and Functions of Murine Hematopoietic Stem Cells.” Stem Cells 31, no. 6 (June 1, 2013): 1202–12. https://doi.org/10.1002/stem.1369.
An N, Lin Y-W, Mahajan S, Kellner JN, Wang Y, Li Z, et al. Pim1 Serine/Threonine Kinase Regulates the Number and Functions of Murine Hematopoietic Stem Cells. Stem Cells. 2013 Jun 1;31(6):1202–12.
An, Ningfei, et al. “Pim1 Serine/Threonine Kinase Regulates the Number and Functions of Murine Hematopoietic Stem Cells.” Stem Cells, vol. 31, no. 6, Oxford University Press (OUP), June 2013, pp. 1202–12. Crossref, doi:10.1002/stem.1369.
An N, Lin Y-W, Mahajan S, Kellner JN, Wang Y, Li Z, Kraft AS, Kang Y. Pim1 Serine/Threonine Kinase Regulates the Number and Functions of Murine Hematopoietic Stem Cells. Stem Cells. Oxford University Press (OUP); 2013 Jun 1;31(6):1202–1212.
Journal cover image

Published In

Stem Cells

DOI

EISSN

1549-4918

ISSN

1066-5099

Publication Date

June 1, 2013

Volume

31

Issue

6

Start / End Page

1202 / 1212

Publisher

Oxford University Press (OUP)

Related Subject Headings

  • Immunology
  • 32 Biomedical and clinical sciences
  • 31 Biological sciences
  • 11 Medical and Health Sciences
  • 10 Technology
  • 06 Biological Sciences