Open AccessEarly growth response 1 regulates hematopoietic support and proliferation in human primary bone marrow stromal cells
Author(s) -
Hongzhe Li,
Hooi-Ching Lim,
Dimitra Zacharaki,
Xiaojie Xian,
Keane Jared Guillaume Kenswil,
Sandro Bräunig,
Marc H.G.P. Raaijmakers,
NielsBjarne Woods,
Jenny Hansson,
Stefan Scheding
Publication year - 2019
Publication title -
haematologica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.782
H-Index - 142
eISSN - 1592-8721
pISSN - 0390-6078
DOI - 10.3324/haematol.2019.216648
Subject(s) - stromal cell , haematopoiesis , bone marrow , egr1 , biology , microbiology and biotechnology , stem cell , cancer research , lymph node stromal cell , transcription factor , cd34 , hematopoietic stem cell , immunology , gene , genetics
Human bone marrow stromal cells (BMSC) are key elements of the hematopoietic environment and they play a central role in bone and bone marrow physiology. However, how key stromal cell functions are regulated is largely unknown. We analyzed the role of the immediate early response transcription factor EGR1 as key stromal cell regulator and found that EGR1 was highly expressed in prospectively-isolated primary BMSC, down-regulated upon culture, and low in non-colony-forming CD45 neg stromal cells. Furthermore, EGR1 expression was lower in proliferative regenerating adult and fetal primary cells compared to adult steady-state BMSC. Overexpression of EGR1 in stromal cells induced potent hematopoietic stroma support as indicated by an increased production of transplantable CD34 + CD90 + hematopoietic stem cells in expansion co-cultures. The improvement in bone marrow stroma support function was mediated by increased expression of hematopoietic supporting genes, such as VCAM1 and CCL28 Furthermore, EGR1 overexpression markedly decreased stromal cell proliferation whereas EGR1 knockdown caused the opposite effects. These findings thus show that EGR1 is a key stromal transcription factor with a dual role in regulating proliferation and hematopoietic stroma support function that is controlling a genetic program to co-ordinate the specific functions of BMSC in their different biological contexts.