【專題演講】9月24日(四)上午9:30「
主題:Engineered HSCs Confer Multipotentiality and Reconstitute Adaptive Immunity
日期:104年09月24日(星期四) 09:30a.m. ~10:30a.m.
地點:勵學大樓2 F第一會議室
內容說明:
本中心擬於104年9月24日(星期四)
Summary of lecture
Hematopoietic stem cell (HSC) transplantation is curative for malignant and genetic blood disorders, but is limited by donor availability and immune mismatch. Deriving HSCs from patient-matched embryonic/pluripotent stem cells (ESC/PSCs) could address these limitations. Prior efforts in a murine model system have exploited enforced expression of hoxb4 to drive self-renewal and enable multi-lineage reconstitution of irradiated hosts by ESC-HSCs, yet fell short in delivering robust lymphoid engraftment. Analysis of the gene regulatory networks of hoxb4-ESC-HSC revealed a deficiency in targets of the Notch signal transduction pathway. Here, by titrating exposure of hoxb4-ESC-HSC to Notch ligands, we report derivation of engineered HSCs that self-
renew, repopulate multi-lineage hematopoiesis in primary and secondary engrafted mice, and endow adaptive immunity in immune-deficient recipients. Single cell analysis shows that following engraftment in the bone marrow niche, these engineered HSCs further specify to a hybrid cell-type in which distinct gene regulatory networks of hematopoietic stem/progenitors and differentiated hematopoietic lineages are co-expressed. Our work demonstrates engineering of fully functional HSCs via modulation of genetic programs that govern self-renewal (via HoxB4) and lineage priming (via Notch pathway activation).
演講時間、地點
日 期:104年09月24日(星期四) 09:30~10:30
地 點:勵學大樓 2F 第一會議室
(高雄市三民區十全一路100號)
主辦單位:高雄醫學大學–脂質科學暨老化研究中心
聯絡人:脂質科學暨老化研究中心 / 詹秀娟
聯絡電話 07-3121101轉2294
E-mail: lsarc@kmu.edu.tw