کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8341131 | 1541283 | 2015 | 10 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
A novel population of local pericyte precursor cells in tumor stroma that require Notch signaling for differentiation
ترجمه فارسی عنوان
یک جمعیت جدید از سلول های پیش ساز محلی پروتئین در استروما تومور که نیچ را برای تمایز نیاز دارند
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موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
چکیده انگلیسی
Pericytes are perivascular support cells, the origin of which in tumor tissue is not clear. Recently, we identified a Tie1+ precursor cell that differentiates into vascular smooth muscle, in a Notch-dependent manner. To understand the involvement of Notch in the ontogeny of tumor pericytes we used a novel flow immunophenotyping strategy to define CD146+/CD45â/CD31â/lo pericytes in the tumor stroma. This strategy combined with ex vivo co-culture experiments identified a novel pericyte progenitor cell population defined as Sca1hi/CD146â/CD45â/CD31â. The differentiation of these progenitor cells was stimulated by co-culture with endothelial cells. Overexpression of the Notch ligand Jagged1 in endothelial cells further stimulated the differentiation of Sca1hi/CD146â/CD45â/CD31â cells into pericytes, while inhibition of Notch signaling with a γ-secretase inhibitor reduced this differentiation. However, Notch inhibition specifically in Tie1-expressing cells did not change the abundance of pericytes in tumors, suggesting that the pericyte precursor is distinct from the vascular smooth muscle cell precursor. Transplant experiments showed that the bone marrow contributes minimally to tumor pericytes. Immunophenotyping revealed that Sca1hi/CD146â/CD45â/CD31â cells have greater potential to differentiate into pericytes and have increased expression of classic mesenchymal stem cell markers (CD13, CD44, Nt5e and Thy-1) compared to Sca1â/lo/CD146â/CD45â/CD31â cells. Our results suggest that a local Sca1hi/CD146â/CD45â/CD31â pericyte progenitor resides in the tumor microenvironment and requires Notch signaling for differentiation into mature pericytes.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Microvascular Research - Volume 101, September 2015, Pages 38-47
Journal: Microvascular Research - Volume 101, September 2015, Pages 38-47
نویسندگان
Alexandre Patenaude, Stefan Woerher, Patricia Umlandt, Fred Wong, Rawa Ibrahim, Alastair Kyle, Sandy Unger, Megan Fuller, Jeremy Parker, Andrew Minchinton, Connie J. Eaves, Aly Karsan,