The Stem Cell Niche

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Disruption of Bis Leads to the Deterioration of the Vascular Niche for Hematopoietic Stem Cells†‡§

  1. Kyung-rim Kwon1,
  2. Ji-Yeon Ahn1,
  3. Myung-Shin Kim1,
  4. Joo-Young Jung1,
  5. Jeong-Hwa Lee2,
  6. Il-Hoan Oh1,¶,*

Article first published online: 18 DEC 2009

DOI: 10.1002/stem.285

Issue

STEM CELLS

STEM CELLS

Volume 28, Issue 2, pages 268–278, February 2010

Additional Information

How to Cite

Kwon, K.-r., Ahn, J.-Y., Kim, M.-S., Jung, J.-Y., Lee, J.-H. and Oh, I.-H. (2010), Disruption of Bis Leads to the Deterioration of the Vascular Niche for Hematopoietic Stem Cells. STEM CELLS, 28: 268–278. doi: 10.1002/stem.285

Author Information

  1. 1

    Catholic Cell Therapy Center & Department of Cellular Medicine, The Catholic University of Korea, Seoul, Korea

  2. 2

    Department of Biochemistry, The Catholic University of Korea, Seoul, Korea

  1. Telephone: 82-2-2258-8268; Fax: 82-2-591-3994

*Catholic High-Performance Cell Therapy Center, The Catholic University of Korea, 505 Banpo-Dong, Seocho-Ku, Seoul, Korea 137-701

  1. †

    Author contributions: K.R.K. and J.Y.A.: Performed research, collected data, prepared manuscript figure; K.R.K. and J.Y.A. made equal contribution to this study; M.S.K.: Performed research, collected data, interpreted data; J.Y.J.: Performed research, designed research; J.H.L.: Performed research, produced animal model; I.H.O.: Designed research, analyzed and interpreted data, wrote the manuscript.

  2. ‡

    Disclosure of potential conflicts of interest is found at the end of this article.

  3. §

    First published online in STEM CELLSEXPRESS January 28, 2010.

Publication History

  1. Issue published online: 16 FEB 2010
  2. Article first published online: 18 DEC 2009
  3. Accepted manuscript online: 18 DEC 2009 12:00AM EST
  4. Manuscript Accepted: 1 DEC 2009
  5. Manuscript Received: 3 JUN 2009

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Keywords:

  • Hematopoietic stem cell;
  • bis;
  • Vascular niche

Abstract

The stem cell niche plays an important role in the microenvironmental regulation of hematopoietic stem cells, but the integration of niche activity remains poorly understood. In this study, we show that a functional deficiency of Bis/BAG-3/CAIR-1, a protein related to apoptosis and the response to cellular stress, results in perturbation of the vascular stem cell niche, causing a series of hematopoietic derangements. Mice with a targeted disruption of bis (bis−/−) exhibited a loss of hematopoietic stem cells and defective B-cell development. However, this hematological defect of bis−/− mice was not reproduced when bis−/− bone marrow cells were transplanted into bis+/+ recipients. Moreover, bis+/+ bone marrow cells, when transplanted into bis−/− mice, reproduced the same defect as bis−/− cells, pointing to the microenvironmental origin of the phenotypes. Subsequent analysis of bis−/− mice bone marrow revealed a characteristic defect in the vascular stem cell niche that included the defective growth of stromal progenitor cells in colony forming unit-fibroblasts, the defect in sinusoidal endothelium, and the loss of stromal cells expressing CXCL-12 or IL-7 in the bone marrow. In contrast, no abnormalities were observed in the growth and hematopoietic supporting activities of osteoblasts from bis−/− mice bone marrows. Collectively, these results indicate that Bis functions to mediate cellular regulation of the stem cell niche on the vascular compartment and suggest that the vascular and osteoblastic compartments of the stem cell niche can be independently regulated during the in vivo orchestration of hematopoiesis. STEM CELLS 2010;28:268–278

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