Endothelial protein C receptor-expressing hematopoietic stem cells reside in the perisinusoidal niche in fetal liver

Hiroko Iwasaki, Fumio Arai, Yoshiaki Kubota, Maria Dahl, Toshio Suda

Research output: Contribution to journalArticle

54 Citations (Scopus)

Abstract

Hematopoietic stem cells (HSCs) are maintained in specialized niches in adult bone marrow. However, niche and HSC maintenance mechanism in fetal liver (FL) still remains unclear. Here, we investigated the niche and the molecular mechanism of HSC maintenance in mouse FL using HSCs expressing endothelial protein C receptor (EPCR). The antiapoptotic effect of activated protein C (APC) on EPCR+ HSCs and the expression of protease-activated receptor 1 (Par-1) mRNA in these cells suggested the involvement of the cytoprotective APC/ EPCR/Par-1 pathway in HSC maintenance. Immunohistochemistry revealed that EPCR+ cells were localized adjacent to, or integrated in, the Lyve-1+ sinusoidal network, whereAPC and extracellular matrix (ECM) are abundant, suggesting that HSCs in FL were maintained in the APC- and ECM-rich perisinusoidal niche. EPCR+ HSCs were in a relatively slow cycling state, consistent with their high expression levels of p57 and p18. Furthermore, the long-term reconstitution activity of EPCR+ HSCs decreased significantly after short culture but not when cocultured with feeder layer of FL-derived Lyve-1+ cells, which suggests that the maintenance of the self-renewal activity of FL HSCs largely depended on the interaction with the perisinusoidal niche. In conclusion, EPCR+ HSCs resided in the perisinusoidal niche in mouse FL.

Original languageEnglish
Pages (from-to)544-553
Number of pages10
JournalBlood
Volume116
Issue number4
DOIs
Publication statusPublished - 2010 Jul 29

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Hematopoietic Stem Cells
Protein C
Stem cells
Liver
PAR-1 Receptor
Maintenance
Extracellular Matrix
Feeder Cells
Fetal Movement
Cell culture
Bone
Bone Marrow
Immunohistochemistry
Messenger RNA

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

Cite this

Endothelial protein C receptor-expressing hematopoietic stem cells reside in the perisinusoidal niche in fetal liver. / Iwasaki, Hiroko; Arai, Fumio; Kubota, Yoshiaki; Dahl, Maria; Suda, Toshio.

In: Blood, Vol. 116, No. 4, 29.07.2010, p. 544-553.

Research output: Contribution to journalArticle

Iwasaki, Hiroko ; Arai, Fumio ; Kubota, Yoshiaki ; Dahl, Maria ; Suda, Toshio. / Endothelial protein C receptor-expressing hematopoietic stem cells reside in the perisinusoidal niche in fetal liver. In: Blood. 2010 ; Vol. 116, No. 4. pp. 544-553.
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