In research utilizing induced pluripotent stem cells (iPSCs), we aim to elucidate the molecular mechanisms governing the differentiation process from limb bud mesenchymal cells (LBM) to bone. A central objective of this study is to deepen our understanding of how branching points in human skeletal development, together with the precise temporal and spatial coordination of signaling cues, elicit intracellular changes that drive lineage specification. To address this challenge, we employ data science approaches, with a particular emphasis on multi-omics analysis.
Research focus
- Identification of differentiation-associated genes and their regulatory mechanisms
During the differentiation of iPSCs into LBM, and subsequently from LBM into chondrocytes, we seek to identify genes involved in lineage commitment and to clarify the mechanisms regulating their expression. Gene transcription is dependent on an open chromatin configuration, and histone chemical modifications play a critical role in modulating transcriptional activity. By interrogating these processes, we analyze the mechanisms underlying dynamic changes in gene expression during differentiation. - An integrated approach using multi-omics analyses
We employ a broad range of multi-omics methodologies, including bulk RNA sequencing (bulk RNA-seq), ATAC sequencing (ATAC-seq), chromatin immunoprecipitation sequencing (ChIP-seq), and CUT&Tag. By integratively analyzing datasets obtained from these complementary perspectives, we gain access to previously unrecognized biological phenomena and mechanisms that have been difficult to dissect using conventional approaches, thereby achieving a deeper molecular-level understanding of developmental processes.
Utilization of bioinformatics and supercomputing resources
The large-scale datasets generated through our research are processed using bioinformatics approaches. To this end, we develop original data-processing and analytical tools that leverage supercomputing resources, as well as novel computational algorithms tailored to our research questions. These efforts enable comprehensive and rapid analyses of complex biological phenomena, leading to the discovery of new insights.
Medical applications
By elucidating the molecular mechanisms underlying human skeletal development, we aim to translate our findings into future medical applications. Ultimately, this work is expected to contribute to the advancement of cutting-edge therapeutic strategies and regenerative medicine, and to support the development of novel treatments for a wide range of diseases.