دورية أكاديمية

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

التفاصيل البيبلوغرافية
العنوان: Early growth response 1 regulates hematopoietic support and proliferation in human primary bone marrow stromal cells
المؤلفون: Li, Hongzhe, Lim, Hooi Ching, Zacharaki, Dimitra, Xian, Xiaojie, Kenswil, Keane Jg, Bräunig, Sandro, Raaijmakers, Marc Hgp, Woods, Niels-Bjarne, Hansson, Jenny, Scheding, Stefan
المصدر: Haematologica; 105(5), pp 1206-1215 (2020) ; ISSN: 1592-8721
بيانات النشر: Ferrata Storti Foundation
سنة النشر: 2020
المجموعة: Lund University Publications (LUP)
مصطلحات موضوعية: Hematology
الوصف: 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.
نوع الوثيقة: article in journal/newspaper
اللغة: English
العلاقة: https://lup.lub.lu.se/record/26f82a72-dcb8-4fdd-91a5-c5dc7694b9a3Test; http://dx.doi.org/10.3324/haematol.2019.216648Test; scopus:85086236064; pmid:31371413
DOI: 10.3324/haematol.2019.216648
الإتاحة: https://doi.org/10.3324/haematol.2019.216648Test
https://lup.lub.lu.se/record/26f82a72-dcb8-4fdd-91a5-c5dc7694b9a3Test
رقم الانضمام: edsbas.124A15E9
قاعدة البيانات: BASE