Diabetes Induces a Transcriptional Signature in Bone Marrow–Derived CD34+ Hematopoietic Stem Cells Predictive of Their Progeny Dysfunction

Autor: Gualtiero I. Colombo, Veronica Ricci, Erica Rurali, Vera Vigorelli, Giulio Pompilio, Mattia Chiesa, Angela Raucci, Yuri D'Alessandra, Maria Cristina Vinci
Jazyk: angličtina
Rok vydání: 2021
Předmět:
0301 basic medicine
Male
Chemokine
Lymphocyte
CD34
Antigens
CD34
Coronary Artery Disease
lcsh:Chemistry
Cohort Studies
0302 clinical medicine
Myeloid Cells
CD34+
transcriptional profile
Lymphocytes
lcsh:QH301-705.5
Spectroscopy
biology
diabetes
Cell Differentiation
General Medicine
Middle Aged
Computer Science Applications
Haematopoiesis
medicine.anatomical_structure
Phenotype
Cardiovascular Diseases
Female
Stem cell
bone marrow
030209 endocrinology & metabolism
Catalysis
Article
Inorganic Chemistry
Diabetes Complications
03 medical and health sciences
medicine
Humans
Physical and Theoretical Chemistry
Progenitor cell
Molecular Biology
Aged
Innate immune system
Blood Cells
Gene Expression Profiling
Organic Chemistry
hematopoietic stem cells
030104 developmental biology
lcsh:Biology (General)
lcsh:QD1-999
inflammation
biology.protein
Cancer research
Bone marrow
Transcriptome
Zdroj: International Journal of Molecular Sciences
Volume 22
Issue 3
International Journal of Molecular Sciences, Vol 22, Iss 1423, p 1423 (2021)
ISSN: 1422-0067
DOI: 10.3390/ijms22031423
Popis: Hematopoietic stem/progenitor cells (HSPCs) participate in cardiovascular (CV) homeostasis and generate different types of blood cells including lymphoid and myeloid cells. Diabetes mellitus (DM) is characterized by chronic increase of pro-inflammatory mediators, which play an important role in the development of CV disease, and increased susceptibility to infections. Here, we aimed to evaluate the impact of DM on the transcriptional profile of HSPCs derived from bone marrow (BM). Total RNA of BM-derived CD34+ stem cells purified from sternal biopsies of patients undergoing coronary bypass surgery with or without DM (CAD and CAD-DM patients) was sequenced. The results evidenced 10566 expressed genes whose 79% were protein-coding genes, and 21% non-coding RNA. We identified 139 differentially expressed genes (p-value <
0.05 and |log2 FC| >
0.5) between the two comparing groups of CAD and CAD-DM patients. Gene Set Enrichment Analysis (GSEA), based on Gene Ontology biological processes (GO-BP) terms, led to the identification of fourteen overrepresented biological categories in CAD-DM samples. Most of the biological processes were related to lymphocyte activation, chemotaxis, peptidase activity, and innate immune response. Specifically, HSPCs from CAD-DM patients displayed reduced expression of genes coding for proteins regulating antibacterial and antivirus host defense as well as macrophage differentiation and lymphocyte emigration, proliferation, and differentiation. However, within the same biological processes, a consistent number of inflammatory genes coding for chemokines and cytokines were up-regulated. Our findings suggest that DM induces transcriptional alterations in HSPCs, which are potentially responsible of progeny dysfunction.
Databáze: OpenAIRE
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