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

Author:

Cao JiaORCID,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-YuanORCID,Liu Zheng-ZhaoORCID,Wang Zhen-XingORCID,Xie HuiORCID

Abstract

AbstractEndothelial 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.

Funder

National Natural Science Foundation of China

Publisher

Springer Science and Business Media LLC

Subject

General Physics and Astronomy,General Biochemistry, Genetics and Molecular Biology,General Chemistry,Multidisciplinary

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