Dataset Information

EGR1 regulation in human bone marrow stromal cells

ABSTRACT: Human bone marrow stromal cells (BMSCs) are key elements of the hematopoietic environment and they play a central role in bone and bone marrow physiology. However, how key BMSC functions are regulated is largely unknown. We analyzed the role of the immediate early response transcription factor EGR1 as key BMSC regulator and found that EGR1 was highly expressed in prospectively-isolated primary BMSCs, downregulated upon culture, and lower in non-CFU-F-containing CD45neg BM cells. Furthermore, EGR1 expression was lower in proliferative regenerating adult and fetal primary cells compared to adult steady-state BMSCs. Accordingly, EGR1 overexpression markedly decreased BMSC proliferation but considerably improved hematopoietic stroma support function as indicated by an increased production of transplantable CD34+CD90+ hematopoietic stem cells in expansion co-cultures. The improvement of BMSC stroma support function was mediated by increased expression of hematopoietic supporting genes, such as VCAM1 and CCL28. On the other hand, EGR1 knockdown increased ROS-mediated BMSC proliferation, and clearly reduced BMSC hematopoietic stroma support potential. These findings thus show that EGR1 is a key BMSC transcription factor with a dual role in regulating proliferation and hematopoietic stroma support function that is controlling a genetic program to coordinate the specific functions of BMSC in their different biological contexts.

INSTRUMENT(S): Orbitrap Fusion

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Mesenchymal Stem Cell Of The Bone Marrow, Bone Marrow

SUBMITTER: Jenny Hansson

LAB HEAD: Jenny Hansson

PROVIDER: PXD011767 | Pride | 2019-06-27

REPOSITORIES: Pride

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Early growth response 1 regulates hematopoietic support and proliferation in human primary bone marrow stromal cells.

Li Hongzhe H Lim Hooi-Ching HC Zacharaki Dimitra D Xian Xiaojie X Kenswil Keane J G KJG Bräunig Sandro S Raaijmakers Marc H G P MHGP Woods Niels-Bjarne NB Hansson Jenny J Scheding Stefan S

Haematologica 20190801 5

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<sup>neg</sup> stro ...[more]

PMID: 31371413

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