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RNA-based Reprogramming of Human Primary Fibroblasts into Induced Pluripotent Stem Cells
Published on: November 26, 2018
Large intergenic non-coding RNA-RoR modulates reprogramming of human induced pluripotent stem cells.
Sabine Loewer1, Moran N Cabili, Mitchell Guttman
1Stem Cell Transplantation Program, Division of Pediatric Hematology and Oncology, Manton Center for Orphan Disease Research, Children's Hospital Boston and Dana Farber Cancer Institute, Boston, Massachusetts, USA.
Nature Genetics
|November 9, 2010
Summary
Researchers identified large intergenic non-coding RNAs (lincRNAs) crucial for reprogramming cells into induced pluripotent stem cells (iPSCs). One lincRNA, lincRNA-RoR, directly influences this stem cell derivation process.
Area of Science:
- Stem cell biology
- Epigenetics
- Non-coding RNA research
Background:
- Cellular reprogramming to induced pluripotent stem cells (iPSCs) involves significant epigenetic and gene expression changes.
- Large intergenic non-coding RNAs (lincRNAs) are increasingly recognized for their roles in cellular processes, but their function in pluripotency remains largely unexplored.
Purpose of the Study:
- To investigate the transcriptional landscape of lincRNAs during human iPSC derivation.
- To identify specific lincRNAs associated with pluripotency and their potential roles in reprogramming.
Main Methods:
- Transcriptional profiling of human iPSCs and embryonic stem cells.
- Bioinformatic analysis to identify lincRNAs linked to pluripotency.
- Functional studies using loss-of-function and gain-of-function approaches for specific lincRNAs.
Main Results:
- Numerous lincRNAs were identified with expression patterns linked to pluripotency.
- Ten lincRNAs showed elevated expression in iPSCs compared to embryonic stem cells, suggesting a role in iPSC emergence.
- These lincRNAs were found to be direct targets of key pluripotency transcription factors.
- The lincRNA-RoR was demonstrated to modulate the reprogramming process.
Conclusions:
- lincRNAs play a significant role in the transcriptional reorganization during iPSC derivation.
- Specific lincRNAs, such as lincRNA-RoR, are critical regulators of cellular reprogramming.
- This study provides the first evidence for essential functions of lincRNAs in generating pluripotent stem cells.
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