Polyploidization of murine mesenchymal cells is associated with suppression of the long noncoding RNA H19 and reduced tumorigenicity
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Updated: May 17, 2026

Proliferation and Differentiation of Murine Myeloid Precursor 32D/G-CSF-R Cells
Published on: February 21, 2018
Ofer Shoshani1, Hassan Massalha, Nir Shani
1Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel.
Abstract:
Mesenchymal stromal cells (MSC) are used extensively in clinical trials; however, the possibility that MSCs have a potential for malignant transformation was raised. We examined the genomic stability versus the tumor-forming capacity of multiple mouse MSCs. Murine MSCs have been shown to be less stable and more prone to malignant transformation than their human counterparts. A large series of independently isolated MSC populations exhibited low tumorigenic potential under syngeneic conditions, which increased in immunocompromised animals. Unexpectedly, higher ploidy correlated with reduced tumor-forming capacity. Furthermore, in both cultured MSCs and primary hepatocytes, polyploidization was associated with a dramatic decrease in the expression of the long noncoding RNA H19. Direct knockdown of H19 expression in diploid cells resulted in acquisition of polyploid cell traits. Moreover, artificial tetraploidization of diploid cancer cells led to a reduction of H19 levels, as well as to an attenuation of the tumorigenic potential. Polyploidy might therefore serve as a protective mechanism aimed at reducing malignant transformation through the involvement of the H19 regulatory long noncoding RNA.
Insights
Mesenchymal stromal cells (MSCs) showed reduced tumor formation with higher ploidy. Polyploidization, linked to decreased H19 long noncoding RNA, may protect against malignant transformation.
Area of Science:
- Cell Biology
- Genomics
- Cancer Research
Background:
- Mesenchymal stromal cells (MSCs) are widely used in clinical trials.
- Concerns exist regarding the potential for MSC malignant transformation.
- Murine MSCs exhibit greater genomic instability than human MSCs.
Purpose of the Study:
- To investigate the relationship between genomic stability and tumor-forming capacity in mouse MSCs.
- To explore the role of polyploidy and H19 long noncoding RNA in MSC tumorigenesis.
Main Methods:
- Examined genomic stability and tumor-forming capacity of multiple mouse MSC populations.
- Assessed the correlation between cell ploidy and tumorigenic potential.
- Investigated the expression of H19 long noncoding RNA in polyploid cells and its functional role via knockdown and artificial tetraploidization.
Main Results:
- Mouse MSCs demonstrated low tumorigenic potential in syngeneic hosts, increasing in immunocompromised animals.
- Higher cell ploidy unexpectedly correlated with reduced tumor-forming capacity.
- Polyploidization in MSCs and hepatocytes was associated with decreased H19 expression.
- H19 knockdown induced polyploid cell traits; artificial tetraploidization reduced H19 levels and tumorigenicity in cancer cells.
Conclusions:
- Polyploidy may act as a protective mechanism against malignant transformation in MSCs.
- The H19 long noncoding RNA is implicated in the regulatory pathway linking polyploidy to reduced tumorigenesis.
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