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

Iwasaki, Hiroko; Arai, Fumio; Kubota, Yoshiaki; Dahl, Maria LU and Suda, Toshio (2010) In Blood 116(4). p.544-553
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, where APC and extracellular matrix (ECM) are... (More)
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, where APC 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. (Blood. 2010; 116(4): 544-533) (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Blood
volume
116
issue
4
pages
544 - 553
publisher
American Society of Hematology
external identifiers
  • wos:000280502800010
  • scopus:77956054189
ISSN
1528-0020
DOI
10.1182/blood-2009-08-240903
language
English
LU publication?
yes
id
b304fe1c-dc86-46f6-b1cc-802753157ccb (old id 1654587)
date added to LUP
2010-08-26 14:58:36
date last changed
2018-06-17 03:34:42
@article{b304fe1c-dc86-46f6-b1cc-802753157ccb,
  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, where APC 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. (Blood. 2010; 116(4): 544-533)},
  author       = {Iwasaki, Hiroko and Arai, Fumio and Kubota, Yoshiaki and Dahl, Maria and Suda, Toshio},
  issn         = {1528-0020},
  language     = {eng},
  number       = {4},
  pages        = {544--553},
  publisher    = {American Society of Hematology},
  series       = {Blood},
  title        = {Endothelial protein C receptor-expressing hematopoietic stem cells reside in the perisinusoidal niche in fetal liver},
  url          = {http://dx.doi.org/10.1182/blood-2009-08-240903},
  volume       = {116},
  year         = {2010},
}