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

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

  • Nat Commun. 2023 Dec 20;14(1):8461. doi: 10.1038/s41467-023-44312-w.
Jia Cao 1 2 3,  Ling Jin 1 2,  Zi-Qi Yan 1,  Xiao-Kai Wang 1,  You-You Li 1 2,  Zun Wang 1,  Yi-Wei Liu 1 2,  Hong-Ming Li 1 2,  Zhe Guan 1 2,  Ze-Hui He 1 2,  Jiang-Shan Gong 1 2,  Jiang-Hua Liu 1,  Hao Yin 1 2,  Yi-Juan Tan 1 2,  Chun-Gu Hong 1 2,  Shi-Kai Feng 1,  Yan Zhang 1,  Yi-Yi Wang 1 2,  Lu-Yue Qi 1,  Chun-Yuan Chen 1 2 3,  Zheng-Zhao Liu 1 2 3,  Zhen-Xing Wang 4 5 6,  Hui Xie 7 8 9
Affiliations

Affiliations

  • 1 Department of Orthopedics, Movement System Injury and Repair Research Center, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China.
  • 2 Hunan Key Laboratory of Angmedicine, Changsha, Hunan, 410008, China.
  • 3 National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China.
  • 4 Department of Orthopedics, Movement System Injury and Repair Research Center, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China. wangzx@csu.edu.cn.
  • 5 Hunan Key Laboratory of Angmedicine, Changsha, Hunan, 410008, China. wangzx@csu.edu.cn.
  • 6 National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China. wangzx@csu.edu.cn.
  • 7 Department of Orthopedics, Movement System Injury and Repair Research Center, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China. huixie@csu.edu.cn.
  • 8 Hunan Key Laboratory of Angmedicine, Changsha, Hunan, 410008, China. huixie@csu.edu.cn.
  • 9 National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China. huixie@csu.edu.cn.
PMID: 38123537 DOI: 10.1038/s41467-023-44312-w
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.

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