患有血液疾病或免疫缺陷的病人需要骨髓移植。無論如何，移植需要合適的人類白血球抗原的來源。而且即便在治療後，病人還是需要長期服用抗排斥藥物。因此，一個合適的人類白血球抗原的來源是令人嚮往的。從病人自體分化而來的誘導性多功能幹細胞(induced pluripotent stem cells,iPSCs)可以讓我們達到這個目標。無論如何，獲得分化的血球前驅細胞(blood precursors)的方法還沒被確認。這裡我們建立了一個穩定的系統，藉由最佳化胞外因子的類型和濃度而從誘導性多功能幹細胞和胚胎幹細胞獲得造血內皮細胞(hemogenic endothelium)和血球前驅細胞。接著我們藉由將血球前驅細胞與基質細胞共同培養後確認了一個適合驅使淋巴細胞形成的環境。我們發現如同胞外因子的劑量，不同的基質細胞也和分化的效率有關係。不同的造血內皮細胞和血球前驅細胞表現不同的細胞表面抗原和分化成淋巴球的能力。相同的作用在多株的誘導性多功能幹細胞和胚胎幹細胞都已經被觀察到。簡言之，我們產生具有T淋巴球能力的造血內皮細胞和血球前驅細胞。這在未來對於機轉的了解和治療方法將會有幫助的。

Patients with blood diseases or immunity defects need bone marrow transplantation. However, Transplantation requires compatible source of human leukocyte antigen (HLA). Even after treatment, the patients have to take life-long anti-rejection drugs. Thus, a source of HLA-compatible blood precursors is highly desirable. The goal could be achieved by differentiating induced pluripotent stem cells (iPSCs) from the isogenic patients. However, the methodology of obtaining differentiated blood precursors remain undefined. Here we established a stable system of acquiring hemogenic endothelium and blood precursors from iPSCs/ESCs by optimizing the types and concentrations of extracellular factors. Subsequently, we defined a suitable environment of driving lymphoid cells from blood precursors by co-culturing with stromal cells. We found that there was a relationship between the differentiation efficiency and the types of feeder cells as well as the dosages of extracellular factors. Different hemogenic endothelium and blood precursors expressed different cell surface markers and differed in lymphogenic potential. The same effect had been observed in multiple hES/hiPS cell lines. In sum, we were able to generate hemogenic endothelium and blood precursors with T-lympoid potential in vitro. It will be helpful for mechanical understanding and therapeutics in the future.

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