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Related Concept Videos

Alternative RNA Splicing02:18

Alternative RNA Splicing

Alternative RNA splicing is the regulated splicing of exons and introns to produce different mature mRNAs from a single pre-mRNA. Unlike in constitutive splicing where a single gene produces a single type of mRNA, alternative splicing allows an organism to produce multiple proteins from a single gene and plays an important role in protein diversity.
There are five types of alternative RNA splicing that vary in the ways the pre-mRNA segments are removed or retained in the mature mRNA. The first...
Maintenance of the ES Cell State01:14

Maintenance of the ES Cell State

The cells of the blastocyst inner cell mass only remain pluripotent for a short time. This state of pluripotency and self-renewal can be maintained in embryonic stem (ES) cell culture by adding specific chemicals or growth factors to ensure the cells can continue dividing and later differentiate into different cell types. In some cases, the cells are grown on a feeder layer of differentiated cells, which provides the growth factors and extracellular matrix components necessary for stem cell...
RNA Splicing01:32

RNA Splicing

Splicing is the process by which eukaryotic RNA is edited before its translation into protein. The RNA strand transcribed from eukaryotic DNA is called the primary transcript. The primary transcripts that become mRNAs are called precursor messenger RNAs (pre-mRNAs). Eukaryotic pre-mRNA contains alternating sequences of exons and introns. Exons are nucleotide sequences that code for proteins, whereas introns are the non-coding regions. In RNA splicing, introns are removed and exons are bonded...
Methods of Nuclear Reprogramming01:24

Methods of Nuclear Reprogramming

Nuclear reprogramming is a process of transforming one cell type into an unrelated cell type by epigenetic changes that alter the cell’s original gene expression pattern. Such epigenetic changes force cells to express a different set of genes, which play a significant role in inducing transformation into other cell types. Nuclear reprogramming offers applications in reproductive cloning for livestock propagation and regenerative medicine — developing patient-specific cells for injury repair.
Somatic to iPS Cell Reprogramming01:29

Somatic to iPS Cell Reprogramming

Reprogramming alters the gene expression in somatic cells, transforming them into induced pluripotent stem (iPS) cells over several generations. Scientists can reprogram cells by introducing genes for four transcription factors—Oct4, Sox2, Klf4, and c-Myc (OSKM) by viral or non-viral methods. These factors are also known as Yamanaka factors after Shinya Yamanaka, who first generated iPS cells using mouse skin cells. Yamanaka was awarded the Nobel Prize in Physiology or Medicine in 2012 for this...

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Related Experiment Video

Updated: Jun 12, 2026

Generation of Mice Derived from Induced Pluripotent Stem Cells
11:56

Generation of Mice Derived from Induced Pluripotent Stem Cells

Published on: November 29, 2012

Alternative splicing regulates mouse embryonic stem cell pluripotency and differentiation.

Nathan Salomonis1, Christopher R Schlieve, Laura Pereira

  • 1Gladstone Institute of Cardiovascular Disease, San Francisco, CA 94158, USA.

Proceedings of the National Academy of Sciences of the United States of America
|May 26, 2010
PubMed
Summary

Alternative splicing (AS) plays a critical role in embryonic stem cell (ES cell) differentiation. This study identified numerous AS variants impacting protein function and revealed their involvement in key cellular pathways, aiding regenerative medicine.

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Structure-function Studies in Mouse Embryonic Stem Cells Using Recombinase-mediated Cassette Exchange
15:13

Structure-function Studies in Mouse Embryonic Stem Cells Using Recombinase-mediated Cassette Exchange

Published on: April 27, 2017

Area of Science:

  • * Stem Cell Biology
  • * Molecular Biology
  • * Regenerative Medicine

Background:

  • * Regenerative medicine aims to reprogram somatic cells to pluripotency and control differentiation.
  • * Understanding RNA isoforms generated by alternative splicing (AS) and alternative promoter selection (APS) is crucial for advancing these goals.
  • * Alternative splicing and promoter selection significantly influence cellular function and development.

Purpose of the Study:

  • * To investigate the genome-wide roles of alternative splicing (AS) and alternative promoter selection (APS) in differentiating mouse embryonic stem cells (ES cells).
  • * To identify and characterize novel RNA isoform variants and their functional implications.
  • * To demonstrate the utility of the AltAnalyze software for global functional analysis of AS.

Main Methods:

  • * Genome-wide interrogation of reciprocal exon-exon junctions in differentiating mouse ES cells using a prototype Affymetrix microarray.
  • * Analysis of RNA isoform variants using the open-source software package AltAnalyze.
  • * Functional characterization of alternative isoforms for Serca2 and Tcf3 genes, including microRNA targeting and transcriptional repression analysis.

Main Results:

  • * Identified 144 genes with 170 putative isoform variants, with 67% predicted to alter protein sequence or domain composition.
  • * Verified alternative exons were predominantly linked to Wnt signaling and cell-cycle control pathways and showed conservation between mouse and human.
  • * Alternative Serca2 isoforms were targeted by specific microRNAs (miRNA-200b, miRNA-214), indicating a role in cardiac development.
  • * Knockdown of a specific Tcf3 isoform revealed distinct transcriptional repression targets and differentiation outcomes in ES cells.

Conclusions:

  • * Alternative splicing plays a critical role in the specification and differentiation of embryonic stem cells.
  • * The identified alternative splicing events are conserved and impact key cellular pathways.
  • * Global functional analysis of alternative splicing, facilitated by tools like AltAnalyze, is essential for understanding cell differentiation and advancing regenerative medicine.