Skip to main content

Lund University Publications

LUND UNIVERSITY LIBRARIES

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

Li, Hongzhe LU ; Lim, Hooi Ching LU ; Zacharaki, Dimitra LU ; Xian, Xiaojie LU ; Kenswil, Keane Jg ; Bräunig, Sandro LU ; Raaijmakers, Marc Hgp ; Woods, Niels-Bjarne LU ; Hansson, Jenny LU orcid and Scheding, Stefan LU (2020) In Haematologica 105(5). p.1206-1215
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... (More)

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.

(Less)
Please use this url to cite or link to this publication:
author
; ; ; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Haematologica
volume
105
issue
5
pages
10 pages
publisher
Ferrata Storti Foundation
external identifiers
  • pmid:31371413
  • scopus:85086236064
ISSN
1592-8721
DOI
10.3324/haematol.2019.216648
language
English
LU publication?
yes
additional info
Copyright © 2019, Ferrata Storti Foundation.
id
26f82a72-dcb8-4fdd-91a5-c5dc7694b9a3
date added to LUP
2019-11-25 13:38:42
date last changed
2025-03-21 13:36:48
@article{26f82a72-dcb8-4fdd-91a5-c5dc7694b9a3,
  abstract     = {{<p>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.</p>}},
  author       = {{Li, Hongzhe and Lim, Hooi Ching and Zacharaki, Dimitra and Xian, Xiaojie and Kenswil, Keane Jg and Bräunig, Sandro and Raaijmakers, Marc Hgp and Woods, Niels-Bjarne and Hansson, Jenny and Scheding, Stefan}},
  issn         = {{1592-8721}},
  language     = {{eng}},
  number       = {{5}},
  pages        = {{1206--1215}},
  publisher    = {{Ferrata Storti Foundation}},
  series       = {{Haematologica}},
  title        = {{Early growth response 1 regulates hematopoietic support and proliferation in human primary bone marrow stromal cells}},
  url          = {{http://dx.doi.org/10.3324/haematol.2019.216648}},
  doi          = {{10.3324/haematol.2019.216648}},
  volume       = {{105}},
  year         = {{2020}},
}