202102,KogaSaori

研究発表を行った学会；JSDB Online Trial Meeting 2020
2020年9月24-25日　（オンライン）
タイトル； Establishment of culture system for the induction of hematopoietic stem cells from mouse embryonic precursors.
発表者；古賀 沙緒里氏
（熊本大学　発生医学研究所　組織幹細胞分野）
要旨；
Definitive hematopoietic stem cells (HSCs) develop from hemogenic endothelial cells (HECs) located in the aorta-gonad-mesonephros (AGM) region of the mouse embryo. Differentiation of HSCs from HECs takes place between embryonic day (E) 9.5 and E11.5. The differentiation process goes through several intermediate stages including the precursor of HSC type I (preHSC-I), which is defined as CD45-VE-cadherin+CD41+ cell population. While preHSC-I is not yet able to repopulate bone marrow hematopoiesis of irradiated adult recipient mice, previous reports have revealed that transplantable HSCs can be generated from preHSC-I in OP9 stromal cell co-aggregation culture supplemented with three cytokines. However, the OP9 co-aggregation culture has failed to induce HSCs from HECs. In this study, we aimed to establish culture systems for the induction of HSCs from early embryonic precursors. We succeeded to induce transplantable HSCs from E10.5 CD45-VE-cadherin+CD41- cells by mixing bEnd.3 endothelial cells into the OP9 co-aggregation culture. Consequently, the modified culture condition was capable of supporting the differentiation of HSCs not only from preHSC-I but also from HECs present in E10.5 mouse embryos. Furthermore, we succeeded to induce HSCs from E11.5 preHSC-I even in a serum-free and feeder-free culture condition. These culture systems should be useful to investigate the molecular mechanisms underlying the differentiation of HSCs from HECs for the purpose of inducing transplantable HSCs from pluripotent stem cell lines.