中文摘要:
通过化学重编程技术将人体体细胞诱导为巨核细胞,是研发新型替代血小板来源的优质策略。本团队在前期红细胞向巨核细胞化学重编程实验方案的基础上,建立了一套稳定高效的诱导体系,成功利用来源更为丰富的人脐血CD3+T细胞诱导产生诱导型巨核细胞。该体系采用包含重编程增效剂AZD4205的五小分子组合配方,可清除T细胞固有细胞特征,助力细胞向巨核细胞谱系发生命运转换。
经T细胞诱导获得的诱导型巨核细胞,具备巨核细胞典型的细胞形态与分子特征,能够生成前血小板并释放具备正常生理功能的血小板。单细胞RNA测序结果进一步证实,诱导型巨核细胞存在细胞异质性,可分为增殖周期型、免疫特征型、血小板生成偏向型等功能亚型。本研究优化了化学重编程策略,实现了T细胞向巨核细胞的高效谱系转换,为制备临床级巨核细胞与功能性血小板提供了简便、可行的全新技术手段。
英文摘要:
The generation of megakaryocytes (MKs) from human somatic cells through chemical reprogramming represents a promising strategy for developing alternative platelet sources. Building on our prior chemical reprogramming protocol for converting erythroblasts to MKs, we established a robust method that successfully generated induced MKs (iMKs) from human cord blood–derived CD3+ T cells, which is a more abundant source. This method used a five–small molecule cocktail containing a reprogramming booster, AZD4205, to promote erasure of T cell identity and facilitate fate transition toward MKs. T cell–derived iMKs exhibited characteristic MK cellular and molecular signatures, demonstrating the capacity to produce proplatelets and release functional platelets. Single-cell RNA sequencing further revealed that iMKs were heterogeneous with distinct functional profiles, including cycling, immune, and thrombopoiesis-biased MKs. Our findings highlight an optimized chemical reprogramming strategy that enables efficient conversion of T cells to MKs, providing a practical and convenient approach to generating clinically relevant MKs and platelets.
论文信息:
论文题目:Efficient chemical reprogramming of human T cells into functional megakaryocytes and platelets
期刊名称:Science Advances
时间期卷:Vol 12, Issue29(2026)
在线时间:2026年7月15日
DOI: 10.1126/sciadv.aeb31
产品信息:
货号:CP-005-005
规格:5ml+5ml
品牌:Liposoma
产地:荷兰
名称:Clodronate Liposomes&Control Liposomes
办事处:靶点科技
Clodronate Liposomes氯膦酸盐脂质体清除经Day-7辐照的免疫缺陷小鼠体内巨噬细胞。荷兰Liposoma巨噬细胞清除剂ClodronateLiposomes见刊于Science Advances:高效化学重编程人T细胞为功能性巨核细胞与血小板。

Liposoma巨噬细胞清除剂Clodronate Liposomes氯膦酸二钠脂质体清除巨噬细胞的材料和方法:
In vivo macrophage depletion
On day −7, 8- to 12-week-old male NVSG mice (Viewsolid Biotech Co. Ltd., Beijing, China) were irradiated (2.5 Gy) to induce thrombocytopenia. On day −1, the mice were depleted of macrophages by treatment with 0.04 mg of clodronate liposomes (Liposoma Technology, Amsterdam, Netherlands) per gram of mouse weight. iMKs were stained with 5 μM DiD (Thermo Fisher Scientific, V22887) for 20 min at 37°C before washing. PBS (400 μl) containing 1 × 107 cells was injected into mice through the tail vein. Human platelets were monitored by flow cytometry from peripheral blood samples at 1, 3, 6, 9, and 24 hours after transfusion using antibodies specific for human CD41a. The absolute platelet count was determined using a Mindray Bc-2800 Vet Blood Cell Counter (Mindray, Shenzhen, China). The mice were euthanized 24 hours after transfusion, and samples from the spleen, bone marrow, and lungs were collected. All mice were kept under specific pathogen–free conditions, and all procedures were performed according to protocols approved by the Institutional Animal Care and Use Committee at the Institute of Radiation Medicine.
巨噬细胞清除材料和方法文献截图:高效化学重编程人T细胞为功能性巨核细胞与血小板
