Seminars

TBX1 (T-box transcription factor 1) is the major causative gene for congenital heart defects in patients with 22q11.2 deletion syndrome. It is highly expressed in cardio-pharyngeal mesoderm (CPM) cells in the pharyngeal apparatus that form the branchiomeric muscles (BrM) and cardiac outflow tract (OFT) at mouse embryonic day E8.0 -E10.5 when the heart is formed. After cells migrate to the OFT, Tbx1 expression disappears. Tbx1 global null as well as mesodermal (Mesp1-Cre) conditional knockout embryos exhibited a persistent truncus arteriosus, which is a major OFT defect. To understand Tbx1 functions in cell fate decisions of CPM cells, we performed single cell RNA-sequencing (scRNA-seq) of FACS purified Mesp1-Cre;GFP+ and Tbx1-Cre;GFP+ positive cells from embryos at E9.5. We identified 5 clusters as CPM lineage, that are from both Mesp1-Cre+ and Tbx1+ lineages. In addition to BrM, OFT, INF (inflow tract) and SM (somitic mesoderm) populations, we identified a novel multi-lineage progenitor (MLPs) cell population, expressing genes of different CPM cell fates and it has the branches toward BrM, IFT and SMs in cell trajectory analysis.  Tbx1 is expressed in BrM and MLPs, but not in the differentiated cardiac cells. We also performed scRNA-seq on Tbx1 cKO mouse  embryos of Mesp1+ and Tbx1+ lineages. Tbx1 cKO datasets of Mesp1+ and Tbx1+ lineages had same clusters as control dataset, but the ratio of MLPs are increased in Tbx1 cKO datasets.  This result suggests Tbx1 regulates differentiation toward three different branches.

 能丸先生は九州大学大学院をご修了後ニューヨークに移られ、Barnice Morrow教授のもとで心臓発生におけるT-box型転写因子の役割を研究されています。今回は、分子生物学会年会に出席される機会を利用して本学にお立ち寄りいただきます。In vivoにおける単細胞の遺伝子発現解析や心臓発生における細胞運命決定の分子機構について、最新の知見をお聞きできるチャンスです。奮ってご参加ください。なおセミナーは英語で行われますが、質問は日本語・英語でご対応いただけます。