Project description:Transcription factor (TF) networks are pivotal in regulating the fate of stem/progenitor cells. However, the intricate regulatory mechanisms mediated by key TFs in adult periosteal stem/progenitor cells (PSPCs) remain poorly understood, hindering the development of targeted therapies for craniofacial bone regeneration. Here, we show that the imprinted TF PLAGL1 is critical for osteoblast differentiation in PSPCs. Furthermore, we identify that PLAGL1 transcriptionally activates TF Irx5 in collaboration with TF KLF4, which, in turn, induces the expression of downstream osteogenic genes.
Project description:Transcription factor (TF) networks are pivotal in regulating the fate of stem/progenitor cells. However, the intricate regulatory mechanisms mediated by key TFs in adult periosteal stem/progenitor cells (PSPCs) remain poorly understood, hindering the development of targeted therapies for craniofacial bone regeneration. Here, we show that the imprinted TF PLAGL1 is critical for osteoblast differentiation in PSPCs. Furthermore, we identify that PLAGL1 transcriptionally activates TF Irx5 in collaboration with TF KLF4, which, in turn, induces the expression of downstream osteogenic genes.
Project description:Bone development and repair depends on the differentiation of mesenchymal stem cells (MSCs) into osteoblasts. MSCs can be differentiated towards osteoblasts in vitro, making these cells a convenient tool for investigation of osteogenesis. Molecular characterization of this process is relevant for the application of MSCs in skeletal regenerative medicine, and for understanding the deregulation of osteogenesis in bone disease. Cellular differentiation is driven by highly regulated changes in gene expression, which at the level of transcription is associated with DNA binding of transcriptional regulators and local changes in chromatin landscape. By sequencing of RNA (RNA-Seq) and immunoprecipitated chromatin (ChIP-Seq) we have characterized gene expression, histone modification changes and DNA binding of the bone master regulator RUNX2 in osteogenic differentiation. Data from the RNA-Seq experiment has also been deposited at ArrayExpress under accession number E-MTAB-1829 (https://www.ebi.ac.uk/arrayexpress/experiments/E-MTAB-1829/).
