Knockdown of N-cadherin suppresses the long-term engraftment of hematopoietic stem cells

Kentaro Hosokawa, Fumio Arai, Hiroki Yoshihara, Hiroko Iwasaki, Yuka Nakamura, Yumiko Gomei, Toshio Suda

Research output: Contribution to journalArticle

83 Citations (Scopus)

Abstract

During postnatal life, the bone marrow (BM) supports both self-renewal and differentiation of hematopoietic stem cells (HSCs) in specialized microenvironments termed stem cell niches. Cell-cell and cell-extracellular matrix interactions between HSCs and their niches are critical for the maintenance of HSC properties. Here, we analyzed the function of Ncadherin in the regulation of the proliferation and long-term repopulation activity of hematopoietic stem/progenitor cells (HSPCs) by the transduction of N-cadherin shRNA. Inhibition of N-cadherin expression accelerated cell division in vitro and reduced the lodgment of donor HSPCs to the endosteal surface, resulting in a significant reduction in long-term engraftment. Cotransduction of N-cadherin shRNA and a mutant N-cadherin that introduced the silent mutations to shRNA target sequences rescued the accelerated cell division and reconstitution phenotypes. In addition, the requirement of N-cadherin for HSPC engraftment appears to be niche specific, as shN-cad-transduced lineage-Sca- 1+c-Kit+ cells successfully engrafted in spleen, which lacks an osteoblastic niche. These findings suggest that N-cad-mediated cell adhesion is functionally required for the establishment of hematopoiesis in the BM niche after BM transplantation.

Original languageEnglish
Pages (from-to)554-563
Number of pages10
JournalBlood
Volume116
Issue number4
DOIs
Publication statusPublished - 2010 Jul 29

Fingerprint

Cadherins
Hematopoietic Stem Cells
Stem cells
Small Interfering RNA
Bone
Stem Cell Niche
Cell Division
Cells
Bone Marrow
Cell adhesion
Hematopoiesis
Bone Marrow Transplantation
Cell Adhesion
Extracellular Matrix
Spleen
Maintenance
Phenotype

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

Cite this

Hosokawa, K., Arai, F., Yoshihara, H., Iwasaki, H., Nakamura, Y., Gomei, Y., & Suda, T. (2010). Knockdown of N-cadherin suppresses the long-term engraftment of hematopoietic stem cells. Blood, 116(4), 554-563. https://doi.org/10.1182/blood-2009-05-224857

Knockdown of N-cadherin suppresses the long-term engraftment of hematopoietic stem cells. / Hosokawa, Kentaro; Arai, Fumio; Yoshihara, Hiroki; Iwasaki, Hiroko; Nakamura, Yuka; Gomei, Yumiko; Suda, Toshio.

In: Blood, Vol. 116, No. 4, 29.07.2010, p. 554-563.

Research output: Contribution to journalArticle

Hosokawa, K, Arai, F, Yoshihara, H, Iwasaki, H, Nakamura, Y, Gomei, Y & Suda, T 2010, 'Knockdown of N-cadherin suppresses the long-term engraftment of hematopoietic stem cells', Blood, vol. 116, no. 4, pp. 554-563. https://doi.org/10.1182/blood-2009-05-224857
Hosokawa K, Arai F, Yoshihara H, Iwasaki H, Nakamura Y, Gomei Y et al. Knockdown of N-cadherin suppresses the long-term engraftment of hematopoietic stem cells. Blood. 2010 Jul 29;116(4):554-563. https://doi.org/10.1182/blood-2009-05-224857
Hosokawa, Kentaro ; Arai, Fumio ; Yoshihara, Hiroki ; Iwasaki, Hiroko ; Nakamura, Yuka ; Gomei, Yumiko ; Suda, Toshio. / Knockdown of N-cadherin suppresses the long-term engraftment of hematopoietic stem cells. In: Blood. 2010 ; Vol. 116, No. 4. pp. 554-563.
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