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

Research output: Contribution to journalArticle

Abstract

Human bone marrow stromal cells 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 bone marrow stromal cells, downregulated upon culture, and low in non-colony-forming CD45neg stromal cells. Furthermore, EGR1 expression was lower in proliferative regenerating adult and fetal primary cells compared to adult steady-state bone marrow stromal cells. 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 of 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 coordinate the specific functions of bone marrow stromal cells in their different biological contexts.

Details

Authors
Organisations
External organisations
  • Erasmus University Medical Center
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Hematology
Original languageEnglish
Pages (from-to)1206-1215
Number of pages10
JournalHaematologica
Volume105
Issue number5
Early online date2019 Aug 1
Publication statusPublished - 2020 May
Publication categoryResearch
Peer-reviewedYes

Bibliographic note

Copyright © 2019, Ferrata Storti Foundation.