Department of Orthopedics, Movement System Injury and Repair Research Center, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China.
Hunan Key Laboratory of Angmedicine, Changsha, Hunan, 410008, China.
Nat Commun. 2023 Dec 20;14(1):8461. doi: 10.1038/s41467-023-44312-w.
Endothelial cells (ECs) and bone marrow stromal cells (BMSCs) play crucial roles in supporting hematopoiesis and hematopoietic regeneration. However, whether ECs are a source of BMSCs remains unclear. Here, we evaluate the contribution of endothelial-to-mesenchymal transition to BMSC generation in postnatal mice. Single-cell RNA sequencing identifies ECs expressing BMSC markers Prrx1 and Lepr; however, this could not be validated using Prrx1-Cre and Lepr-Cre transgenic mice. Additionally, only a minority of BMSCs are marked by EC lineage tracing models using Cdh5-rtTA-tetO-Cre or Tek-CreERT2. Moreover, Cdh5 BMSCs and Tek BMSCs show distinct spatial distributions and characteristic mesenchymal markers, suggestive of their origination from different progenitors rather than CDH5 TEK ECs. Furthermore, myeloablation induced by 5-fluorouracil treatment does not increase Cdh5 BMSCs. Our findings indicate that ECs hardly convert to BMSCs during homeostasis and myeloablation-induced hematopoietic regeneration, highlighting the importance of using appropriate genetic models and conducting careful data interpretation in studies concerning endothelial-to-mesenchymal transition.
内皮细胞（ECs）和骨髓基质细胞（BMSCs）在支持造血和造血再生中发挥着至关重要的作用。然而，内皮细胞是否是 BMSCs 的来源尚不清楚。在这里，我们评估了内皮细胞向间充质细胞转化对出生后小鼠 BMSC 生成的贡献。单细胞 RNA 测序鉴定出表达 BMSC 标志物 Prrx1 和 Lepr 的 ECs；然而，这无法通过 Prrx1-Cre 和 Lepr-Cre 转基因小鼠得到验证。此外，只有少数 BMSCs 被 Cdh5-rtTA-tetO-Cre 或 Tek-CreERT2 等内皮谱系追踪模型标记。此外，Cdh5 BMSCs 和 Tek BMSCs 表现出不同的空间分布和特征性间充质标志物，提示它们起源于不同的祖细胞，而不是 CDH5 TEK ECs。此外，5-氟尿嘧啶处理引起的骨髓清除不会增加 Cdh5 BMSCs。我们的研究结果表明，在内稳态和骨髓清除诱导的造血再生过程中，内皮细胞几乎不会转化为 BMSCs，这突出了在涉及内皮细胞向间充质细胞转化的研究中使用适当的遗传模型和仔细解释数据的重要性。
