An integrative bioinformatics approach to decipher adipocyte-induced transdifferentiation of osteoblast

• Published in: Genomics (San Diego, Calif.) Vol. 114; no. 4; p. 110422
• Main Authors: Salmi, Ayyoub, Quacquarelli, Federica, Chauveau, Christophe, Clabaut, Aline, Broux, Odile
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 01.07.2022; Elsevier
• Subjects: Adipocyte; Cellular crosstalk; Human bone marrow stromal cells; Life Sciences; Multi-omics; Osteoblast; Transdifferentiation; Osteoblast; Adipocyte; Cellular crosstalk; Transdifferentiation; Human bone marrow stromal cells; Multi-omics
• ISSN: 0888-7543; 1089-8646
• DOI: 10.1016/j.ygeno.2022.110422

In human, bone loss is associated with increased marrow adipose tissue and recent data suggest that medullary adipocytes could play a role in osteoporosis by acting on neighboring bone-forming osteoblasts. Supporting this hypothesis, we previously showed, in a coculture model based on human bone marrow stromal cells, that factors secreted by adipocytes induced the conversion of osteoblasts towards an adipocyte-like phenotype. In this work, we employed an original integrative bioinformatics approach connecting proteomic and transcriptomic data from adipocytes and osteoblasts, respectively, to investigate the mechanisms underlying their crosstalk. Our analysis identified a total of 271 predicted physical interactions between adipocyte-secreted proteins and osteoblast membrane protein coding genes and proposed three pathways for their potential contribution to osteoblast transdifferentiation, the PI3K-AKT, the JAK2-STAT3 and the SMAD pathways. Our findings demonstrated the effectiveness of our integrative omics strategy to decipher cell-cell communication events. •Adipocyte-secreted factors induced the transdifferentiation of osteoblasts.•Adipocyte secretome and osteoblast membranome data were integrated.•Interactions and pathways that may promote osteoblast transdifferentiation were identified.•The integrative bioinformatics approach employed can be extrapolated to other cell types.