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Pleiotrophin regulates the expansion and regeneration of hematopoietic stem cells.

Publication ,  Journal Article
Himburg, HA; Muramoto, GG; Daher, P; Meadows, SK; Russell, JL; Doan, P; Chi, J-T; Salter, AB; Lento, WE; Reya, T; Chao, NJ; Chute, JP
Published in: Nat Med
April 2010

Hematopoietic stem cell (HSC) self-renewal is regulated by both intrinsic and extrinsic signals. Although some of the pathways that regulate HSC self-renewal have been uncovered, it remains largely unknown whether these pathways can be triggered by deliverable growth factors to induce HSC growth or regeneration. Here we show that pleiotrophin, a neurite outgrowth factor with no known function in hematopoiesis, efficiently promotes HSC expansion in vitro and HSC regeneration in vivo. Treatment of mouse bone marrow HSCs with pleiotrophin caused a marked increase in long-term repopulating HSC numbers in culture, as measured in competitive repopulating assays. Treatment of human cord blood CD34(+)CDCD38(-)Lin(-) cells with pleiotrophin also substantially increased severe combined immunodeficient (SCID)-repopulating cell counts in culture, compared to input and cytokine-treated cultures. Systemic administration of pleiotrophin to irradiated mice caused a pronounced expansion of bone marrow stem and progenitor cells in vivo, indicating that pleiotrophin is a regenerative growth factor for HSCs. Mechanistically, pleiotrophin activated phosphoinositide 3-kinase (PI3K) signaling in HSCs; antagonism of PI3K or Notch signaling inhibited pleiotrophin-mediated expansion of HSCs in culture. We identify the secreted growth factor pleiotrophin as a new regulator of both HSC expansion and regeneration.

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Published In

Nat Med

DOI

EISSN

1546-170X

Publication Date

April 2010

Volume

16

Issue

4

Start / End Page

475 / 482

Location

United States

Related Subject Headings

  • Thrombopoietin
  • Stem Cell Factor
  • Signal Transduction
  • Receptors, Notch
  • Phosphatidylinositol 3-Kinases
  • Mice, SCID
  • Mice, Inbred C57BL
  • Mice
  • Immunology
  • Humans
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Himburg, H. A., Muramoto, G. G., Daher, P., Meadows, S. K., Russell, J. L., Doan, P., … Chute, J. P. (2010). Pleiotrophin regulates the expansion and regeneration of hematopoietic stem cells. Nat Med, 16(4), 475–482. https://doi.org/10.1038/nm.2119
Himburg, Heather A., Garrett G. Muramoto, Pamela Daher, Sarah K. Meadows, J Lauren Russell, Phuong Doan, Jen-Tsan Chi, et al. “Pleiotrophin regulates the expansion and regeneration of hematopoietic stem cells.Nat Med 16, no. 4 (April 2010): 475–82. https://doi.org/10.1038/nm.2119.
Himburg HA, Muramoto GG, Daher P, Meadows SK, Russell JL, Doan P, et al. Pleiotrophin regulates the expansion and regeneration of hematopoietic stem cells. Nat Med. 2010 Apr;16(4):475–82.
Himburg, Heather A., et al. “Pleiotrophin regulates the expansion and regeneration of hematopoietic stem cells.Nat Med, vol. 16, no. 4, Apr. 2010, pp. 475–82. Pubmed, doi:10.1038/nm.2119.
Himburg HA, Muramoto GG, Daher P, Meadows SK, Russell JL, Doan P, Chi J-T, Salter AB, Lento WE, Reya T, Chao NJ, Chute JP. Pleiotrophin regulates the expansion and regeneration of hematopoietic stem cells. Nat Med. 2010 Apr;16(4):475–482.

Published In

Nat Med

DOI

EISSN

1546-170X

Publication Date

April 2010

Volume

16

Issue

4

Start / End Page

475 / 482

Location

United States

Related Subject Headings

  • Thrombopoietin
  • Stem Cell Factor
  • Signal Transduction
  • Receptors, Notch
  • Phosphatidylinositol 3-Kinases
  • Mice, SCID
  • Mice, Inbred C57BL
  • Mice
  • Immunology
  • Humans