中国科学院分子细胞科学卓越中心周波、中国科学院大学王前飞、中国医学科学院血液病医院程涛等近日取得一项新成果。经过不懈努力，他们发现了分化途径决定了成人巨核细胞形成的功能输出。该研究于2024年3月5日发表于国际一流学术期刊《免疫》上。

研究团队开发了命运映射系统来区分这两条途径，比较它们的定量和功能输出。课题组人员发现巨核细胞通过两种途径产生，通过这两种途径产生的巨核细胞的产量和动态是可比较的。对命运映射的巨核细胞进行单细胞RNA测序显示，直接和逐步途径分别为支持性生态位和免疫巨核细胞做出了贡献，但共同促进了血小板生成巨核细胞。

来自这两种途径的巨核细胞表现出不同的活性，并受到化疗和炎症的不同调节。他们的工作将分化途径与巨核细胞的异质性联系起来。不同的分化途径导致不同功能的巨核细胞亚群的不同组合，以适应不同的生理需求。

研究人员表示，新的证据揭示了一条造血干细胞向巨核细胞的直接分化途径(直接途径)，经过一系列限制性造血祖细胞的经典分化途径（逐步途径）。这引发了两种不同途径对于巨核造血的重要性的问题。

附：英文原文

Title: Differentiation route determines the functional outputs of adult megakaryopoiesis

Author: Jing-Jing Li, Jingkun Liu, Yunqian Evelyn Li, Lin Veronica Chen, Hui Cheng, Yueying Li, Tao Cheng, Qian-Fei Wang, Bo O. Zhou

Issue&Volume: 2024-03-05

Abstract: Emerging evidence has revealed a direct differentiation route from hematopoietic stem cells to megakaryocytes (direct route), in addition to the classical differentiation route through a series of restricted hematopoietic progenitors (stepwise route). This raises the question of the importance of two alternative routes for megakaryopoiesis. Here, we developed fate-mapping systems to distinguish the two routes, comparing their quantitative and functional outputs. We found that megakaryocytes were produced through the two routes with comparable kinetics and quantity under homeostasis. Single-cell RNA sequencing of the fate-mapped megakaryocytes revealed that the direct and stepwise routes contributed to the niche-supporting and immune megakaryocytes, respectively, but contributed to the platelet-producing megakaryocytes together. Megakaryocytes derived from the two routes displayed different activities and were differentially regulated by chemotherapy and inflammation. Our work links differentiation route to the heterogeneity of megakaryocytes. Alternative differentiation routes result in variable combinations of functionally distinct megakaryocyte subpopulations poised for different physiological demands.

DOI: 10.1016/j.immuni.2024.02.006

Source: https://www.cell.com/immunity/fulltext/S1074-7613(24)00082-7