TY - JOUR
T1 - The characteristics of vessel lining cells in normal spleens and their role in the pathobiology of myelofibrosis
AU - Qiu, Jiajing
AU - Salama, Mohamed E.
AU - Hu, Cing Siang
AU - Li, Yan
AU - Wang, Xiaoli
AU - Hoffman, Ronald
N1 - Publisher Copyright:
© 2018 by The American Society of Hematology.
PY - 2018/5/22
Y1 - 2018/5/22
N2 - The CD342CD8a1, sinusoid lining, littoral cells (LCs), and CD341CD8a2, splenic vascular endothelial cells (SVECs) represent 2 distinct cellular types that line the vessels within normal spleens and those of patients with myelofibrosis (MF). To further understand the respective roles of LCs and SVECs, each was purified from normal and MF spleens, cultured, and characterized. Gene expression profiling indicated that LCs were a specialized type of SVEC. LCs possessed a distinct gene expression profile associated with cytoskeleton regulation, cellular interactions, endocytosis, and iron transport. LCs also were characterized by strong phagocytic activity, less robust tube-forming capacity and a limited proliferative potential. These characteristics underlie the role of LCs as cellular filters and scavengers. Although normal LCs and SVECs produced overlapping as well as distinct hematopoietic factors and adhesion molecules, the gene expression profile of MF LCs and SVECs distinguished them from their normal counterparts. MF SVECs were characterized by activated interferon signaling and cell cycle progression pathways and increased vascular endothelial growth factor receptor, angiopoietin-2, stem cell factor, interleukin (IL)-33, Notch ligands, and IL-15 transcripts. In contrast, the transcription profile of MF LCs was associated with mitochondrial dysfunction, reduced energy production, protein biosynthesis, and catabolism. Normal SVECs formed in vitro confluent cell layers that supported MF hematopoietic colony formation to a greater extent than normal colony formation. These data provide an explanation for the reduced density of LCs observed within MF spleens and indicate the role of SVECs in the development of extramedullary hematopoiesis in MF.
AB - The CD342CD8a1, sinusoid lining, littoral cells (LCs), and CD341CD8a2, splenic vascular endothelial cells (SVECs) represent 2 distinct cellular types that line the vessels within normal spleens and those of patients with myelofibrosis (MF). To further understand the respective roles of LCs and SVECs, each was purified from normal and MF spleens, cultured, and characterized. Gene expression profiling indicated that LCs were a specialized type of SVEC. LCs possessed a distinct gene expression profile associated with cytoskeleton regulation, cellular interactions, endocytosis, and iron transport. LCs also were characterized by strong phagocytic activity, less robust tube-forming capacity and a limited proliferative potential. These characteristics underlie the role of LCs as cellular filters and scavengers. Although normal LCs and SVECs produced overlapping as well as distinct hematopoietic factors and adhesion molecules, the gene expression profile of MF LCs and SVECs distinguished them from their normal counterparts. MF SVECs were characterized by activated interferon signaling and cell cycle progression pathways and increased vascular endothelial growth factor receptor, angiopoietin-2, stem cell factor, interleukin (IL)-33, Notch ligands, and IL-15 transcripts. In contrast, the transcription profile of MF LCs was associated with mitochondrial dysfunction, reduced energy production, protein biosynthesis, and catabolism. Normal SVECs formed in vitro confluent cell layers that supported MF hematopoietic colony formation to a greater extent than normal colony formation. These data provide an explanation for the reduced density of LCs observed within MF spleens and indicate the role of SVECs in the development of extramedullary hematopoiesis in MF.
UR - http://www.scopus.com/inward/record.url?scp=85060321679&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85060321679&partnerID=8YFLogxK
U2 - 10.1182/bloodadvances.2017015073
DO - 10.1182/bloodadvances.2017015073
M3 - Article
C2 - 29776986
AN - SCOPUS:85060321679
SN - 2473-9529
VL - 2
SP - 1130
EP - 1145
JO - Blood Advances
JF - Blood Advances
IS - 10
ER -