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RNA-based Reprogramming of Human Primary Fibroblasts into Induced Pluripotent Stem Cells
Published on: November 26, 2018
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The primate-specific noncoding RNA HPAT5 regulates pluripotency during human preimplantation development and nuclear
Jens Durruthy-Durruthy1,2,3, Vittorio Sebastiano1,2,3, Mark Wossidlo1,2,3
1Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford, California, USA.
Nature Genetics
|November 24, 2015
Summary
Three novel long intergenic noncoding RNAs (lincRNAs) derived from transposable elements (TEs) are crucial for early embryonic development and maintaining pluripotency in human stem cells.
Area of Science:
- Genomics
- Developmental Biology
- RNA Biology
Background:
- Long intergenic noncoding RNAs (lincRNAs) are frequently derived from transposable elements (TEs).
- TE-derived lincRNAs are implicated in pluripotency regulation, but individual functions remain unclear.
- Understanding specific lincRNAs is vital for developmental processes.
Purpose of the Study:
- To characterize three novel TE-derived human lincRNAs: HPAT2, HPAT3, and HPAT5.
- To investigate their roles in preimplantation embryo development and pluripotency.
- To elucidate the molecular mechanisms underlying their function.
Main Methods:
- Loss-of-function experiments in preimplantation embryos.
- CRISPR-mediated gene disruption in pluripotent stem cells.
- Whole-transcriptome analysis and protein-binding assays.
Main Results:
- HPAT2, HPAT3, and HPAT5 are essential for pluripotency acquisition and inner cell mass formation.
- HPAT5 is identified as a key regulator within the pluripotency network.
- HPAT5 interacts with the let-7 microRNA family.
Conclusions:
- Individual TE-derived lincRNAs play unique, critical roles in mammalian development.
- These lincRNAs modulate gene expression to reinforce cell fate during differentiation.
- Primate-specific lincRNA families contribute significantly to developmental regulation.
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