Long Noncoding RNAs in Pluripotency of Stem Cells and Cell Fate Specification

Abstract

Since the annotation of the mouse genome (FANTOM project) [Kawai J et al (2001) Functional annotation of a full-length mouse cDNA collection. Nature 409(6821):685-690] or the human genome [An integrated encyclopedia of DNA elements in the human genome. (2012) Nature 489(7414):57-74; Harrow J et al (2012) GENCODE: the reference human genome annotation for the ENCODE project. Genome Res 22(9):1760-1774], the roles of long noncoding RNAs in coordinating specific signaling pathways have been established in a wide variety of model systems. They have emerged as crucial and key regulators of stem cell maintenance and/or their differentiation into different lineages. In this chapter we have discussed the recently discovered lncRNAs that have been shown to be necessary for the maintenance of pluripotency of both mouse and human ES cells. We have also highlighted the different lncRNAs which are involved in directed differentiation of stem cells into any of the three germ layers. In recent years stem cell therapies including bone marrow transplantation are becoming an integral part of modern medicinal practices. However, there are still several challenges in making stem cell therapy more reproducible so that the success rate reaches a high percentage in the clinic. It is hoped that understanding the molecular mechanisms pertaining to the role of these newly discovered lncRNAs in the differentiation process of stem cells to specific lineages should pave the way to make stem cell therapy and regenerative medicine as a normal clinical practice in the near future.

Competing Endogenous RNAs, Non-Coding RNAs and Diseases: An Intertwined Story

“…Beside the most famous RNA subtypes, such as coding messenger RNAs (mRNAs), transfer RNAs (tRNAs) and ribosomal RNAs (rRNAs), recent research has taken a particular interest in pseudo-genes ( -genes), long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs) [ 6 ]. The non-coding elements have been shown to represent one of the largest portions of transcribed molecules [ 12 , 13 , 14 , 15 ], and to be involved in a very broad set of biological processes [ 16 , 17 , 18 , 19 ], cell-fate programming [ 20 ], aging [ 21 , 22 ] and diseases [ 23 ].…”

Long non-coding RNA in stem cell pluripotency and lineage commitment: functions and evolutionary conservation

“…However, about 1000 human lncRNAs show moderate-to-high expression as well as signs of evolutionary constraint, and around 300 of these are conserved in other non-mammalian vertebrates [ 15 ]. Increasing interest is emerging on lncRNAs in embryonic stem cell biology [ 16 – 18 ]. Here, we present an overview of current knowledge on the functional mechanisms of lncRNA in stem cell pluripotency and lineage commitment, highlighting the importance of evolutionary conservation in this context.…”

GAS5/miR-21 Axis as a Potential Target to Rescue ZCL-082-Induced Autophagy of Female Germline Stem Cells In Vitro

“…Long non-coding RNAs (lncRNAs), which do not encode proteins, can recruit transcription factors and sponge microRNAs (miRNAs) to destabilize mRNA 33, 34, 35, 36. This type of RNA has been found to widely regulate the proliferation, differentiation, apoptosis, and autophagy of stem cells as competing endogenous RNAs (ceRNAs) 37, 38, 39, 40. In our previous study, we determined that growth arrest-specific 5 ( GAS5 ), a lncRNA, promoted proliferation and inhibited apoptosis of FGSCs in vitro ; 21 but, whether and how GAS5 executes other FGSC functions (e.g., autophagy or differentiation) are unclear.…”