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
  • 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. [email protected].
  • 5. Hunan Key Laboratory of Angmedicine, Changsha, Hunan, 410008, China. [email protected].
  • 6. National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China. [email protected].
  • 7. Department of Orthopedics, Movement System Injury and Repair Research Center, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China. [email protected].
  • 8. Hunan Key Laboratory of Angmedicine, Changsha, Hunan, 410008, China. [email protected].
  • 9. National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China. [email protected].
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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