Efficient chemical reprogramming of human T cells into functional megakaryocytes and platelets.

Authors

Jinhua Qin, Zheng Hua, Xingxing Zhao, Jianan Jiang, Jisheng Li, Sihan Wang, Yingwei Pan, Bowen Zhang, Yunqiao Li, Qianqian Zhou, Yiming Zhang, Yanzhou Chen, Yiming Liu, Caiping Xu, Tao Fan, Yang Lv, Xinlong Yan, Wen Yue, Xuetao Pei, Yanhua Li

Published in

Science advances. Volume 12. Issue 29. Pages eaeb3177. Jul 17, 2026. Epub Jul 15, 2026.

Abstract

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.

PMID:
42455952
Bibliographic data and abstract were imported from PubMed on 16 Jul 2026.

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