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A Simple Method to Identify Kinases That Regulate Embryonic Stem Cell Pluripotency by High-throughput Inhibitor Screening
Published on: May 12, 2017
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LIN28 Regulates Stem Cell Metabolism and Conversion to Primed Pluripotency
Jin Zhang1, Sutheera Ratanasirintrawoot1, Sriram Chandrasekaran2
1Stem Cell Transplantation Program, Division of Pediatric Hematology Oncology, Boston Children's Hospital, Boston, MA 02115, USA; Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA.
Cell Stem Cell
|June 21, 2016
Summary
RNA-binding proteins LIN28A and LIN28B are crucial for pluripotency and stem cell reprogramming. They cooperate to regulate cell metabolism and the transition between naive and primed pluripotency states.
Area of Science:
- Stem Cell Biology
- Molecular Biology
- Epigenetics
Background:
- LIN28A and LIN28B are RNA-binding proteins vital for development and cancer.
- Their precise roles in pluripotency and cell reprogramming remain unclear.
Purpose of the Study:
- To elucidate the cooperative functions of LIN28A and LIN28B in cellular reprogramming and pluripotency.
- To investigate the metabolic roles of LIN28 proteins in stem cell states.
Main Methods:
- Reprogramming assays in human and murine cells.
- Analysis of endogenous LIN28A/LIN28B locus reactivation.
- Proteomic and metabolomic analyses.
- mRNA binding assays.
Main Results:
- LIN28B and LIN28A cooperate with key pluripotency factors (NANOG, OCT4, SOX2) for efficient reprogramming.
- Reactivation of both LIN28A and LIN28B loci is essential for maximal reprogramming.
- LIN28 proteins regulate one-carbon and nucleotide metabolism, and histone methylation.
- LIN28 influences mitochondrial function and modulates protein abundance by binding to specific mRNAs.
Conclusions:
- LIN28A and LIN28B play cooperative roles in regulating induced pluripotent stem cell (iPSC) generation.
- These proteins are key regulators of the naive-to-primed pluripotency transition.
- LIN28 proteins are critical for maintaining stem cell metabolism, particularly mitochondrial function.
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