中文摘要:
通過化學(xué)重編程技術(shù)將人體體細(xì)胞誘導(dǎo)為巨核細(xì)胞,是研發(fā)新型替代血小板來源的優(yōu)質(zhì)策略。本團(tuán)隊在前期紅細(xì)胞向巨核細(xì)胞化學(xué)重編程實驗方案的基礎(chǔ)上,建立了一套穩(wěn)定高效的誘導(dǎo)體系,成功利用來源更為豐富的人臍血CD3+T細(xì)胞誘導(dǎo)產(chǎn)生誘導(dǎo)型巨核細(xì)胞。該體系采用包含重編程增效劑AZD4205的五小分子組合配方,可清除T細(xì)胞固有細(xì)胞特征,助力細(xì)胞向巨核細(xì)胞譜系發(fā)生命運轉(zhuǎn)換。
經(jīng)T細(xì)胞誘導(dǎo)獲得的誘導(dǎo)型巨核細(xì)胞,具備巨核細(xì)胞典型的細(xì)胞形態(tài)與分子特征,能夠生成前血小板并釋放具備正常生理功能的血小板。單細(xì)胞RNA測序結(jié)果進(jìn)一步證實,誘導(dǎo)型巨核細(xì)胞存在細(xì)胞異質(zhì)性,可分為增殖周期型、免疫特征型、血小板生成偏向型等功能亞型。本研究優(yōu)化了化學(xué)重編程策略,實現(xiàn)了T細(xì)胞向巨核細(xì)胞的高效譜系轉(zhuǎn)換,為制備臨床級巨核細(xì)胞與功能性血小板提供了簡便、可行的全新技術(shù)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.
論文信息:
論文題目:Efficient chemical reprogramming of human T cells into functional megakaryocytes and platelets
期刊名稱:Science Advances
時間期卷:Vol 12, Issue29(2026)
在線時間:2026年7月15日
DOI: 10.1126/sciadv.aeb31
產(chǎn)品信息:
貨號:CP-005-005
規(guī)格:5ml+5ml
品牌:Liposoma
產(chǎn)地:荷蘭
名稱:Clodronate Liposomes&Control Liposomes
辦事處:靶點科技
Clodronate Liposomes氯膦酸鹽脂質(zhì)體清除經(jīng)Day-7輻照的免疫缺陷小鼠體內(nèi)巨噬細(xì)胞。荷蘭Liposoma巨噬細(xì)胞清除劑ClodronateLiposomes見刊于Science Advances:高效化學(xué)重編程人T細(xì)胞為功能性巨核細(xì)胞與血小板。

Liposoma巨噬細(xì)胞清除劑Clodronate Liposomes氯膦酸二鈉脂質(zhì)體清除巨噬細(xì)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.
巨噬細(xì)胞清除材料和方法文獻(xiàn)截圖:高效化學(xué)重編程人T細(xì)胞為功能性巨核細(xì)胞與血小板


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