Reassessing endothelial-to-mesenchymal transition in mouse bone marrow: insights from lineage tracing models

• Published in: Nature communications Vol. 14; no. 1; p. 8461
• Main Authors: Cao, Jia, Jin, Ling, Yan, Zi-Qi, Wang, Xiao-Kai, Li, You-You, Wang, Zun, Liu, Yi-Wei, Li, Hong-Ming, Guan, Zhe, He, Ze-Hui, Gong, Jiang-Shan, Liu, Jiang-Hua, Yin, Hao, Tan, Yi-Juan, Hong, Chun-Gu, Feng, Shi-Kai, Zhang, Yan, Wang, Yi-Yi, Qi, Lu-Yue, Chen, Chun-Yuan, Liu, Zheng-Zhao, Wang, Zhen-Xing, Xie, Hui
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 20.12.2023; Nature Publishing Group UK; Nature Portfolio
• Subjects: 5-Fluorouracil; Animals; Bone Marrow; Cell culture; Data interpretation; Endothelial Cells; Gene sequencing; Hematopoiesis; Hemopoiesis; Homeostasis; Mesenchymal Stem Cells; Mice; Mice, Transgenic; Regeneration; Spatial distribution; Stromal cells; Tracing; Transgenic mice
• ISSN: 2041-1723; 2041-1723
• 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.