Robo4 Plays a Role in Bone Marrow Homing and Mobilization, but Is Not Essential in the Long-Term Repopulating Capacity of Hematopoietic Stem Cells

Yuko Goto-Koshino, Yumi Fukuchi, Fumi Shibata, Daichi Abe, Kana Kuroda, Shinichiro Okamoto, Toshio Kitamura, Hideaki Nakajima

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Roundabout (Robo) family proteins are immunoglobulin-type surface receptors critical for cellular migration and pathway finding of neuronal axons. We have previously shown that Robo4 was specifically expressed in hematopoietic stem and progenitor cells and its high expression correlated with long-term repopulating (LTR) capacity. To reveal the physiological role of Robo4 in hematopoiesis, we examined the effects of Robo4 disruption on the function of hematopoietic stem cells (HSCs) and progenitors. In Robo4-deficient mice, basic hematological parameters including complete blood cell count and differentiation profile were not affected. In contrast to the previous report, HSC/hematopoietic progenitor (HPC) frequencies in the bone marrow (BM) were perfectly normal in Robo4-/- mice. Moreover, Robo4-/- HSCs were equally competitive as wild-type HSCs in transplantation assays and had normal long-term repopulating (LTR) capacity. Of note, the initial engraftment at 4-weeks after transplantation was slightly impaired by Robo4 ablation, suggesting a marginal defect in BM homing of Robo4-/- HSCs. In fact, homing efficiencies of HSCs/HPCs to the BM was significantly impaired in Robo4-deficient mice. On the other hand, granulocyte-colony stimulating factor-induced peripheral mobilization of HSCs was also impaired by Robo4 disruption. Lastly, marrow recovery from myelosuppressive stress was equally efficient in WT- and Robo4-mutant mice. These results clearly indicate that Robo4 plays a role in HSC trafficking such as BM homing and peripheral mobilization, but is not essential in the LTR and self-renewal capacity of HSCs.

Original languageEnglish
Article numbere50849
JournalPLoS One
Volume7
Issue number11
DOIs
Publication statusPublished - 2012 Nov 30

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Hematopoietic Stem Cells
Stem cells
bone marrow
Bone
Bone Marrow
Blood Cell Count
mice
Hematopoietic Stem Cell Mobilization
hematopoietic stem cells
B-Cell Antigen Receptors
granulocyte colony-stimulating factor
Hematopoietic Stem Cell Transplantation
Hematopoiesis
Granulocyte Colony-Stimulating Factor
blood cell counts
Ablation
cell transplantation
hematopoiesis
Axons
Cell Differentiation

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Robo4 Plays a Role in Bone Marrow Homing and Mobilization, but Is Not Essential in the Long-Term Repopulating Capacity of Hematopoietic Stem Cells. / Goto-Koshino, Yuko; Fukuchi, Yumi; Shibata, Fumi; Abe, Daichi; Kuroda, Kana; Okamoto, Shinichiro; Kitamura, Toshio; Nakajima, Hideaki.

In: PLoS One, Vol. 7, No. 11, e50849, 30.11.2012.

Research output: Contribution to journalArticle

Goto-Koshino, Yuko ; Fukuchi, Yumi ; Shibata, Fumi ; Abe, Daichi ; Kuroda, Kana ; Okamoto, Shinichiro ; Kitamura, Toshio ; Nakajima, Hideaki. / Robo4 Plays a Role in Bone Marrow Homing and Mobilization, but Is Not Essential in the Long-Term Repopulating Capacity of Hematopoietic Stem Cells. In: PLoS One. 2012 ; Vol. 7, No. 11.
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