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Reassessing endothelial-to-mesenchymal transition in mouse bone marrow: insights from lineage tracing models
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Reassessing endothelial-to-mesenchymal transition in mouse bone marrow: insights from lineage tracing models
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Journal Article
Reassessing endothelial-to-mesenchymal transition in mouse bone marrow: insights from lineage tracing models
2023
Overview
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.
Endothelial cells (ECs) and bone marrow stromal cells (BMSCs) support hematopoiesis and hematopoietic regeneration. Whether ECs are a source of BMSCs remains unclear. Here, using lineage tracing models the authors show that ECs are not a source of BMSCs during homeostasis and regeneration.
