FAK Deficiency in Bone Marrow Stromal Cells Alters Their Homeostasis and Drives Abnormal Proliferation and Differentiation of Haematopoietic Stem Cells

Autor: Zhiguo He, Carmen-Mariana Aanei, Emmanuelle Tavernier-Tardy, Gilbert Soglu, Tiphanie Picot, Denis Guyotat, Yuenv Wu, Lydia Campos, Elisabeth Daguenet
Jazyk: angličtina
Rok vydání: 2020
Předmět:
0301 basic medicine
Stromal cell
myelodysplastic syndromes (MDS)
focal adhesion kinase (FAK)
CD34
Biology
haematopoietic stem precursor cell (HSPC)–BMSC interaction
Article
Focal adhesion
lymphocyte function-associated antigen 1 (LFA-1)
03 medical and health sciences
0302 clinical medicine
stomatognathic system
Bone Marrow
hemic and lymphatic diseases
medicine
bone marrow stromal cells (BMSCs)
Homeostasis
Humans
adhesion molecules
CD44
lcsh:QH301-705.5
Aged
Cell Proliferation
Aged
80 and over
Cell adhesion molecule
Cell Differentiation
Mesenchymal Stem Cells
General Medicine
Hematopoietic Stem Cells
Hematopoiesis
Haematopoiesis
030104 developmental biology
medicine.anatomical_structure
lcsh:Biology (General)
030220 oncology & carcinogenesis
Focal Adhesion Protein-Tyrosine Kinases
biology.protein
Cancer research
Bone marrow
Stem cell
Zdroj: Cells
Volume 9
Issue 3
Cells, Vol 9, Iss 3, p 646 (2020)
ISSN: 2073-4409
Popis: Emerging evidence indicates that in myelodysplastic syndromes (MDS), the bone marrow (BM) microenvironment may also contribute to the ineffective, malignant haematopoiesis in addition to the intrinsic abnormalities of haematopoietic stem precursor cells (HSPCs). The BM microenvironment influences malignant haematopoiesis through indirect mechanisms, but the processes by which the BM microenvironment directly contributes to MDS initiation and progression have not yet been elucidated. Our previous data showed that BM-derived stromal cells (BMSCs) from MDS patients have an abnormal expression of focal adhesion kinase (FAK). In this study, we characterise the morpho-phenotypic features and the functional alterations of BMSCs from MDS patients and in FAK knock-downed HS-5 cells. The decreased expression of FAK or its phosphorylated form in BMSCs from low-risk (LR) MDS directly correlates with BMSCs&rsquo
functional deficiency and is associated with a reduced level of haemoglobin. The downregulation of FAK in HS-5 cells alters their morphology, proliferation, and differentiation capabilities and impairs the expression of several adhesion molecules. In addition, we examine the CD34+ healthy donor (HD)-derived HSPCs&rsquo
properties when co-cultured with FAK-deficient BMSCs. Both abnormal proliferation and the impaired erythroid differentiation capacity of HD-HSPCs were observed. Together, these results demonstrate that stromal adhesion mechanisms mediated by FAK are crucial for regulating HSPCs&rsquo
homeostasis.
Databáze: OpenAIRE
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