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

Jia Cao, Ling Jin, Zi-Qi Yan, Xiao-Kai Wang, You-You Li, Zun Wang, Yi-Wei Liu, Hong-Ming Li, Zhe Guan, Ze-Hui He, Jiang-Shan Gong, Jiang-Hua Liu, Hao Yin, Yi-Juan Tan, Chun-Gu Hong, Shi-Kai Feng, Yan Zhang, Yi-Yi Wang, Lu-Yue Qi, Chun-Yuan Chen, Zheng-Zhao Liu, Zhen-Xing Wang () and Hui Xie ()
Additional contact information
Jia Cao: Central South University
Ling Jin: Central South University
Zi-Qi Yan: Central South University
Xiao-Kai Wang: Central South University
You-You Li: Central South University
Zun Wang: Central South University
Yi-Wei Liu: Central South University
Hong-Ming Li: Central South University
Zhe Guan: Central South University
Ze-Hui He: Central South University
Jiang-Shan Gong: Central South University
Jiang-Hua Liu: Central South University
Hao Yin: Central South University
Yi-Juan Tan: Central South University
Chun-Gu Hong: Central South University
Shi-Kai Feng: Central South University
Yan Zhang: Central South University
Yi-Yi Wang: Central South University
Lu-Yue Qi: Central South University
Chun-Yuan Chen: Central South University
Zheng-Zhao Liu: Central South University
Zhen-Xing Wang: Central South University
Hui Xie: Central South University

Nature Communications, 2023, vol. 14, issue 1, 1-15

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.

Date: 2023
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DOI: 10.1038/s41467-023-44312-w

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