Reassessing endothelial-to-mesenchymal transition in mouse bone marrow: insights from lineage tracing models
Jia Cao, Ling Jin, Ziqi Yan, Xiaokai Wang, Youyou Li, Zun Wang, Yi-Wei Liu, Hongmin Li, Zhe Guan, Zehui He, Jiang-Shan Gong, Jianghua Liu, Hao Yin, Yi‐Juan Tan, Chun‐Gu Hong, Shi‐Kai Feng, Yan Zhang, Yiyi Wang, Luyue Qi, Chun‐Yuan Chen, Zhengzhao Liu, Zhen‐Xing Wang, Hui Xie, Zhen‐Xing Wang, Hui Xie
Abstract
Abstract 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.