4.4 Article

EBF1 is expressed in pericytes and contributes to pericyte cell commitment

Journal

HISTOCHEMISTRY AND CELL BIOLOGY
Volume 156, Issue 4, Pages 333-347

Publisher

SPRINGER
DOI: 10.1007/s00418-021-02015-7

Keywords

Pericytes; Angiogenesis; Cell fate commitment; Mesenchymal stem cells

Funding

  1. Universita degli Studi di Brescia within the CRUI-CARE Agreement
  2. Italian Ministry of Health [RF-2016-02361014]
  3. Associazione dedicato A te

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EBF1 plays a significant role in cell fate commitment and is crucial for the expression and function of peri-endothelial cells in vessels. The study found that EBF1 is highly expressed in peri-endothelial cells, which represent bona fide pericytes and are confirmed in human placenta-derived pericytes and human brain vascular pericytes.
Early B-cell factor-1 (EBF1) is a transcription factor with an important role in cell lineage specification and commitment during the early stage of cell maturation. Originally described during B-cell maturation, EBF1 was subsequently identified as a crucial molecule for proper cell fate commitment of mesenchymal stem cells into adipocytes, osteoblasts and muscle cells. In vessels, EBF1 expression and function have never been documented. Our data indicate that EBF1 is highly expressed in peri-endothelial cells in both tumor vessels and in physiological conditions. Immunohistochemistry, quantitative reverse transcription polymerase chain reaction (RT-qPCR) and fluorescence-activated cell sorting (FACS) analysis suggest that EBF1-expressing peri-endothelial cells represent bona fide pericytes and selectively express well-recognized markers employed in the identification of the pericyte phenotype (SMA, PDGFR beta, CD146, NG2). This observation was also confirmed in vitro in human placenta-derived pericytes and in human brain vascular pericytes (HBVP). Of note, in accord with the key role of EBF1 in the cell lineage commitment of mesenchymal stem cells, EBF1-silenced HBVP cells showed a significant reduction in PDGFR beta and CD146, but not CD90, a marker mostly associated with a prominent mesenchymal phenotype. Moreover, the expression levels of VEGF, angiopoietin-1, NG2 and TGF-beta, cytokines produced by pericytes during angiogenesis and linked to their differentiation and activation, were also significantly reduced. Overall, the data suggest a functional role of EBF1 in the cell fate commitment toward the pericyte phenotype.

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