Analyzing the role of primary cilia signaling in controlling adipocyte progenitor fate and function in the bone marrow

• Applicant: Dalila Juliana Silva Ribeiro, Ph.D.
• Subject Area: Hematology, Oncology ; Immunology ; Cell Biology
• Term: since 2022
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 514614027

The bone marrow (BM) niche is a highly complex and specialized space that harbors different cell types, originating from hematopoietic or mesenchymal stem cell (HSC and MSC, respectively) lineages. MSCs differentiate into osteogenic, chondrocyte or adipogenic lineages. The latter composes the BM adipose tissue (BMAd), which is phenotypically distinct from the classic white or brown adipose tissue. BMad exerts endocrine and paracrine functions, regulating the intercellular communication that is fundamental for hematopoiesis or osteogenesis. Primary cilia sense environmental stimuli and transduce them into a cellular response. Primary cilia are only present on adipocyte precursor cells (APCs) and not on mature adipocytes, and have been proposed to regulate adipose tissue homeostasis and expansion. We hypothesize that primary cilia control the function of APCs and, thereby, the intercellular communication between APCs and myeloid cells in the BM niche. In my project, I aim to unravel the role of primary cilia in controlling intercellular communication in the BM niche under physiological and pathological conditions. Methods: I will analyze the role of primary cilia in controlling APC development and function in BMAd by comparing wild-type mice with mice that display primary cilia dysfunction and resemble a ciliopathy, the Bardet-Biedl-Syndrome (Bbs8 -/- mice), which displays obesity as kardinal feature. In parallel to the APC studies, I will investigate myeloid cell differentiation and function in the same mouse models. This will be supported by analyzing gene and protein expression in specific niches within the BMAd. Outlook: This project will help to identify the molecular mechanisms underlying intercellular communication between APCs and myeloid cells in the BM niche and contribute to the understanding of the pathomechanisms causing the Bardet-Biedl Syndrome.

• DFG Programme: WBP Position