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

Li, Hongzhe (author)
Lund University,Lunds universitet,Avdelningen för molekylär hematologi,Institutionen för laboratoriemedicin,Medicinska fakulteten,Stamcellscentrum (SCC),Avdelningen för stamcellsforskning,Benmärgsstamceller och cellulära terapier,Forskargrupper vid Lunds universitet,Division of Molecular Hematology (DMH),Department of Laboratory Medicine,Faculty of Medicine,Stem Cell Center,Division of stem cell research,Bone marrow stem cells and cellular therapies,Lund University Research Groups
Lim, Hooi Ching (author)
Lund University,Lunds universitet,Avdelningen för molekylär hematologi,Institutionen för laboratoriemedicin,Medicinska fakulteten,Stamcellscentrum (SCC),Avdelningen för stamcellsforskning,Benmärgsstamceller och cellulära terapier,Forskargrupper vid Lunds universitet,Division of Molecular Hematology (DMH),Department of Laboratory Medicine,Faculty of Medicine,Stem Cell Center,Division of stem cell research,Bone marrow stem cells and cellular therapies,Lund University Research Groups
Zacharaki, Dimitra (author)
Lund University,Lunds universitet,Avdelningen för molekylär hematologi,Institutionen för laboratoriemedicin,Medicinska fakulteten,Stamcellscentrum (SCC),Avdelningen för stamcellsforskning,Benmärgsstamceller och cellulära terapier,Forskargrupper vid Lunds universitet,Division of Molecular Hematology (DMH),Department of Laboratory Medicine,Faculty of Medicine,Stem Cell Center,Division of stem cell research,Bone marrow stem cells and cellular therapies,Lund University Research Groups
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Xian, Xiaojie (author)
Lund University,Lunds universitet,Avdelningen för molekylärmedicin och genterapi,Institutionen för laboratoriemedicin,Medicinska fakulteten,Blodstamcellsutveckling,Forskargrupper vid Lunds universitet,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Division of Molecular Medicine and Gene Therapy,Department of Laboratory Medicine,Faculty of Medicine,Hematopoietic Stem Cell Development,Lund University Research Groups,LUCC: Lund University Cancer Centre,Other Strong Research Environments
Kenswil, Keane Jg (author)
Erasmus University Medical Center
Bräunig, Sandro (author)
Lund University,Lunds universitet,Avdelningen för molekylär hematologi,Institutionen för laboratoriemedicin,Medicinska fakulteten,Benmärgsstamceller och cellulära terapier,Forskargrupper vid Lunds universitet,Division of Molecular Hematology (DMH),Department of Laboratory Medicine,Faculty of Medicine,Bone marrow stem cells and cellular therapies,Lund University Research Groups
Raaijmakers, Marc Hgp (author)
Erasmus University Medical Center
Woods, Niels-Bjarne (author)
Lund University,Lunds universitet,Avdelningen för molekylärmedicin och genterapi,Institutionen för laboratoriemedicin,Medicinska fakulteten,Blodstamcellsutveckling,Forskargrupper vid Lunds universitet,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Division of Molecular Medicine and Gene Therapy,Department of Laboratory Medicine,Faculty of Medicine,Hematopoietic Stem Cell Development,Lund University Research Groups,LUCC: Lund University Cancer Centre,Other Strong Research Environments
Hansson, Jenny (author)
Lund University,Lunds universitet,Avdelningen för molekylär hematologi,Institutionen för laboratoriemedicin,Medicinska fakulteten,Proteomisk hematologi,Forskargrupper vid Lunds universitet,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Division of Molecular Hematology (DMH),Department of Laboratory Medicine,Faculty of Medicine,Proteomic Hematology,Lund University Research Groups,LUCC: Lund University Cancer Centre,Other Strong Research Environments
Scheding, Stefan (author)
Lund University,Lunds universitet,Avdelningen för molekylär hematologi,Institutionen för laboratoriemedicin,Medicinska fakulteten,Stamcellscentrum (SCC),Avdelningen för stamcellsforskning,Benmärgsstamceller och cellulära terapier,Forskargrupper vid Lunds universitet,Division of Molecular Hematology (DMH),Department of Laboratory Medicine,Faculty of Medicine,Stem Cell Center,Division of stem cell research,Bone marrow stem cells and cellular therapies,Lund University Research Groups
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 (creator_code:org_t)
2019-08-01
2020
English 10 s.
In: Haematologica. - : Ferrata Storti Foundation (Haematologica). - 1592-8721 .- 0390-6078. ; 105:5, s. 1206-1215
Related links:
http://dx.doi.org/10... (free)
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https://doi.org/10.3...
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  • Journal article (peer-reviewed)
Abstract Subject headings
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  • 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.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Hematologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Hematology (hsv//eng)

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