IGF binding protein 2 supports the survival and cycling of hematopoietic stem cells

HoangDinh Huynh, Junke Zheng, Masato Umikawa, Chaozheng Zhang, Robert Silvany, Satoru Iizuka, Martin Holzenberger, Wei Zhang, Chengcheng Zhang

Research output: Contribution to journalArticle

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Abstract

The role of IGF binding protein 2 (IGFBP2) in cell growth is intriguing and largely undefined. Previously we identified IGFBP2 as an extrinsic factor that supports ex vivo expansion of hematopoietic stem cells (HSCs). Here we showed that IGFBP2-null mice have fewer HSCs than wild-type mice. While IGFBP2 has little cell-autonomous effect on HSC function, we found decreased in vivo repopulation of HSCs in primary and secondary transplanted IGFBP2-null recipients. Importantly, bone marrow stromal cells that are deficient for IGFBP2 have significantly decreased ability to support the expansion of repopulating HSCs. To investigate the mechanism by which IGFBP2 supports HSC activity, we demonstrated that HSCs in IGFBP2-null mice had decreased survival and cycling, down-regulated expression of antiapoptotic factor Bcl-2, and up-regulated expression of cell cycle inhibitors p21, p16, p19, p57, and PTEN. Moreover, we found that the C-terminus, but not the RGD domain, of extrinsic IGFBP2 was essential for support of HSC activity. Defective signaling of the IGF type I receptor did not rescue the decreased repopulation of HSCs in IGFBP2- null recipients, suggesting that the environmental effect of IGFBP2 on HSCs is independent of IGF-IR mediated signaling. Therefore, as an environmental factor, IGFBP2 supports the survival and cycling of HSCs.

Original languageEnglish (US)
Pages (from-to)3236-3243
Number of pages8
JournalBlood
Volume118
Issue number12
DOIs
StatePublished - Sep 22 2011

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Insulin-Like Growth Factor Binding Protein 2
Hematopoietic Stem Cells
Stem cells
IGF Type 1 Receptor
Cell growth
Mesenchymal Stromal Cells
Environmental impact
Cell Cycle

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

Cite this

Huynh, H., Zheng, J., Umikawa, M., Zhang, C., Silvany, R., Iizuka, S., ... Zhang, C. (2011). IGF binding protein 2 supports the survival and cycling of hematopoietic stem cells. Blood, 118(12), 3236-3243. https://doi.org/10.1182/blood-2011-01-331876

IGF binding protein 2 supports the survival and cycling of hematopoietic stem cells. / Huynh, HoangDinh; Zheng, Junke; Umikawa, Masato; Zhang, Chaozheng; Silvany, Robert; Iizuka, Satoru; Holzenberger, Martin; Zhang, Wei; Zhang, Chengcheng.

In: Blood, Vol. 118, No. 12, 22.09.2011, p. 3236-3243.

Research output: Contribution to journalArticle

Huynh, H, Zheng, J, Umikawa, M, Zhang, C, Silvany, R, Iizuka, S, Holzenberger, M, Zhang, W & Zhang, C 2011, 'IGF binding protein 2 supports the survival and cycling of hematopoietic stem cells', Blood, vol. 118, no. 12, pp. 3236-3243. https://doi.org/10.1182/blood-2011-01-331876
Huynh H, Zheng J, Umikawa M, Zhang C, Silvany R, Iizuka S et al. IGF binding protein 2 supports the survival and cycling of hematopoietic stem cells. Blood. 2011 Sep 22;118(12):3236-3243. https://doi.org/10.1182/blood-2011-01-331876
Huynh, HoangDinh ; Zheng, Junke ; Umikawa, Masato ; Zhang, Chaozheng ; Silvany, Robert ; Iizuka, Satoru ; Holzenberger, Martin ; Zhang, Wei ; Zhang, Chengcheng. / IGF binding protein 2 supports the survival and cycling of hematopoietic stem cells. In: Blood. 2011 ; Vol. 118, No. 12. pp. 3236-3243.
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