The characteristics of vessel lining cells in normal spleens and their role in the pathobiology of myelofibrosis

Jiajing Qiu, Mohamed Salama, Cing Siang Hu, Yan Li, Xiaoli Wang, Ronald Hoffman

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

The CD34-CD8α+, sinusoid lining, littoral cells (LCs), and CD34+CD8α-, 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.

Original languageEnglish (US)
Pages (from-to)1130-1145
Number of pages16
JournalBlood Advances
Volume2
Issue number10
DOIs
StatePublished - May 22 2018

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Primary Myelofibrosis
Spleen
Endothelial Cells
Transcriptome
Extramedullary Hematopoiesis
Angiopoietin-2
Interleukin-15
Vascular Endothelial Growth Factor Receptor-2
Stem Cell Factor
Protein Biosynthesis
Gene Expression Profiling
Endocytosis
Cytoskeleton
Interferons
Cell Cycle
Iron
Cell Count
Ligands

ASJC Scopus subject areas

  • Medicine(all)

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The characteristics of vessel lining cells in normal spleens and their role in the pathobiology of myelofibrosis. / Qiu, Jiajing; Salama, Mohamed; Hu, Cing Siang; Li, Yan; Wang, Xiaoli; Hoffman, Ronald.

In: Blood Advances, Vol. 2, No. 10, 22.05.2018, p. 1130-1145.

Research output: Contribution to journalArticle

Qiu, Jiajing ; Salama, Mohamed ; Hu, Cing Siang ; Li, Yan ; Wang, Xiaoli ; Hoffman, Ronald. / The characteristics of vessel lining cells in normal spleens and their role in the pathobiology of myelofibrosis. In: Blood Advances. 2018 ; Vol. 2, No. 10. pp. 1130-1145.
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