| Description of the project: | Adipose stem and progenitor cells (ASPCs) play an important role in the expansion of adipose tissue during obesity via hyperplasia. Recently, we discovered a distinct murine ASPC subpopulation in mouse subcutaneous adipose tissue, characterized by high F3 expression, encoding for CD142. These CD142+ ASPCs are refractory to adipogenesis. Additionally, they provide paracrine signals capable of inhibiting adipogenesis in neighboring adipogenic cells. Hence, these cells were named adipogenesis regulators (Aregs). The secretory factors expressed specifically by Aregs also shift CD142− ASPCs into a non-adipogenic Areg-like state. These observations suggest that the transcriptional identity of Aregs can be dynamically regulated. However, thus far it remains unclear how epigenetics regulate and result in the Areg specific transcriptome and which transcription factors TFs play a role in their transcriptional regulation. During my PhD project, I will use amongst others, adipogenic differentiation assays and multiple omics techniques (ATAC-seq, RNA-seq, and single-cell multiome) to investigate the transcriptional determinants of ASPC subpopulations. Given the impact of NAD+ on the activity of transcriptional cofactors and enzymes regulating chromatin accesibility (such as sirtuins and PARPs), we will also take advantage of our experimental settings to investigate how NAD precursors alter the adipogenic capacity and transcriptional landscape of different ASPC subpopulations. Collectively, this project will help our understanding of the molecular mechanisms governing fat expandability. |
