Long non-coding RNA profiling in Human Adult Renal Progenitor Cells and human renal proximal tubular cells

ABSTRACT: Long non-coding RNA (lncRNA) play an important role in several biological processes including some renal diseases. Nevertheless, little is known on lncRNAs that are expressed in healthy kidney and involved in renal cell homeostasis and development and even less is known about lncRNA involved in the maintenance of human adult renal stem/progenitor cells (ARPCs). ARPCs have been shown to be very important for renal homeostasis and repair processes thanks to their self-renewal and differentiative ability as well as their capacity to secrete different reparative factors depending on the type of damage. Through a whole genome transcriptome screening, we found that the HOTAIR lncRNA is highly expressed in renal progenitors and potentially involved cell cycle and senescence biological processes. We then generated HOTAIR knock-out ARPC lines by CRISPR/Cas9 genome editing and showed that this lncRNA limits the apoptotic process of ARPCs and sustains their proliferative capacity, thus resulting responsible of their self-renewal properties. In addition, we found that the knockout of HOTAIR led to the ARPC senescence and to a significant decrease of the CD133 stem cell marker expression that is an inverse marker of ARPC senescence and can regulate renal tubular repair after the damage. Moreover, 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 RPTECs. The HOTAIR knockout in ARPCs leads to lower α-Klotho levels, comparable to that of RPTECs. Finnally we showed that HOTAIR induces epigenetic silencing of the cell cycle inhibitor p15 through the trimethylation of the histone H3K27. Altogether, these results shed new light on these important renal cells and may support the future development of precision therapies for kidney diseases.

ORGANISM(S): Homo sapiens

SUBMITTER: Fabio Sallustio 

PROVIDER: E-MTAB-11451 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress