What is it about?
Human adult renal stem/progenitor cells (ARPCs) have been shown to be very important for renal homeostasis and repair processes. Through a whole-genome transcriptome screening, we found that the HOTAIR lncRNA is highly expressed in renal progenitors and potentially involved in cell cycle and senescence biological processes. By CRISPR/Cas9 genome editing, we generated HOTAIR knockout ARPC lines and established a key role of this lncRNA in ARPC self-renewal properties by sustaining their proliferative capacity and limiting the apoptotic process. Intriguingly, the HOTAIR knockout led to the ARPC senescence and to a significant decrease in the CD133 stem cell marker expression which is an inverse marker of ARPC senescence and can regulate renal tubular repair after the damage. Furthermore, we found that ARPCs expressed high levels of the α-Klotho anti-aging protein and especially 2.6-fold higher levels compared to that secreted by renal proximal tubular cells (RPTECs). Finally, we showed that HOTAIR exerts its function through the epigenetic silencing of the cell cycle inhibitor p15 inducing the trimethylation of the histone H3K27. Altogether, these results shed new light on the mechanisms of regulation of these important renal cells and may support the future development of precision therapies for kidney diseases.
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Why is it important?
Human adult renal stem/progenitor cells (ARPCs) have been shown to be able to regenerate lengthy segments of renal tubules as well as missing podocytes and are a very promising cell population. Here we show that the long non-coding RNA HOTAIR regulates the aging of ARPCs. It limits apoptosis, promotes the cell proliferation, and regulates the CD133 expression and the secretion of anti-aging protein α-Klotho by histone H3K27 trimethylation and silencing of the cyclin p15. These results shed new light on the mechanisms of regulation of these important renal cells and may support the future development of precision therapies for kidney diseases.
Perspectives
We showed that ARPCs, through high expression of HOTAIR, can secrete high quantities of the anti-aging α-Klotho protein. This may influence the microenvironment in the surrounding tissues and therefore contribute to modulating kidney aging. Klotho’s potential effects on stem cells not only provide new insights into their role in anti-aging processes but could also make a significant contribution to clinical/therapeutic advancement in regenerative medicine.
Fabio Sallustio
Universita degli Studi di Bari Aldo Moro
Read the Original
This page is a summary of: The Long Non-coding RNA HOTAIR Controls the Self-renewal, Cell Senescence, and Secretion of Anti-aging Protein α-Klotho in Human Adult Renal Progenitor Cells, Stem Cells, August 2022, Oxford University Press (OUP),
DOI: 10.1093/stmcls/sxac054.
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