Related Experiment Video

Updated: Apr 2, 2026

A Simple Method to Identify Kinases That Regulate Embryonic Stem Cell Pluripotency by High-throughput Inhibitor Screening
07:18

A Simple Method to Identify Kinases That Regulate Embryonic Stem Cell Pluripotency by High-throughput Inhibitor Screening

Published on: May 12, 2017

6.9K

A Src inhibitor regulates the cell cycle of human pluripotent stem cells and improves directed differentiation

Sundari Chetty1, Elise N Engquist2, Elie Mehanna2

  • 1Department of Stem Cell and Regenerative Biology, Harvard Stem Cell Institute, Cambridge, MA 02138 schetty@mcb.harvard.edu dmelton@harvard.edu.

The Journal of Cell Biology
|September 30, 2015
PubMed

Insights

A Src inhibitor, PP1, enhances human pluripotent stem cell (hPSC) differentiation into all three germ layers by regulating cell cycle and retinoblastoma protein activity. This improves subsequent differentiation stages.

Area of Science:

  • Stem cell biology
  • Cell cycle regulation
  • Developmental biology

Background:

  • Directing human pluripotent stem cells (hPSCs) toward specific lineages is difficult.
  • Understanding molecular mechanisms controlling hPSC differentiation is crucial for regenerative medicine.

Purpose of the Study:

  • To investigate the role of Src kinase in regulating hPSC differentiation.
  • To explore the potential of Src inhibition as a strategy to enhance hPSC differentiation efficiency.

Main Methods:

  • Utilized a potent Src inhibitor, PP1, to treat hPSCs.
  • Assessed gene expression related to cell cycle progression (G1 to S phase).
  • Analyzed the activity of retinoblastoma (Rb) proteins.
  • Quantified differentiation into all three germ layers.

Main Results:

  • PP1 treatment modulated cell cycle gene expression.
  • Src inhibition activated retinoblastoma proteins.
  • PP1 treatment significantly increased hPSC differentiation into ectoderm, mesoderm, and endoderm.
  • Genetic suppression of Src yielded similar differentiation enhancements.
  • Improved differentiation efficiency was observed in later differentiation stages.

Conclusions:

  • Src kinase activity negatively impacts hPSC differentiation potential.
  • Inhibiting Src kinase, pharmacologically or genetically, enhances hPSC differentiation across all germ layers.
  • Targeting Src signaling offers a promising approach to improve stem cell differentiation protocols for therapeutic applications.

More Related Videos

Alternative Cultures for Human Pluripotent Stem Cell Production, Maintenance, and Genetic Analysis08:27

Alternative Cultures for Human Pluripotent Stem Cell Production, Maintenance, and Genetic Analysis

Published on: July 24, 2014

13.0K
RNA-based Reprogramming of Human Primary Fibroblasts into Induced Pluripotent Stem Cells11:38

RNA-based Reprogramming of Human Primary Fibroblasts into Induced Pluripotent Stem Cells

Published on: November 26, 2018

11.2K

Related Concept Videos

Chromatin Modification in iPS Cells01:32

Chromatin Modification in iPS Cells

Chromatin modification alters gene expression; therefore, scientists can add histone-modifying enzymes, histone variants, and chromatin remodeling complexes to somatic cells to aid reprogramming into pluripotent stem (iPS) cells.
Compact chromatin makes reprogramming difficult. Enzymes, such as histone demethylases and acetyltransferases, are often added during reprogramming to loosen the chromatin, making the DNA more accessible to transcription factors. Molecules that inhibit histone...
2.3K
Induced Pluripotent Stem Cells01:13

Induced Pluripotent Stem Cells

Stem cells are undifferentiated cells that divide and produce different types of cells. Ordinarily, cells that have differentiated into a specific cell type are post-mitotic—that is, they no longer divide. However, scientists have found a way to reprogram these mature cells so that they “de-differentiate” and return to an unspecialized, proliferative state. These cells are also pluripotent like embryonic stem cells—able to produce all cell types—and are therefore...
28.6K
Induced Pluripotent Stem Cells01:06

Induced Pluripotent Stem Cells

Stem cells are undifferentiated cells that divide and produce different cell types. Ordinarily, cells that have differentiated into a specific cell type are terminally differentiated; however, scientists have found a way to reprogram these mature cells so that they dedifferentiate and return to an unspecialized, proliferative state. These cells are pluripotent like embryonic stem cells—able to produce all cell types—and are called induced pluripotent stem cells (iPSCs).
Somatic...
6.3K
Induced Pluripotent Stem Cells01:13

Induced Pluripotent Stem Cells

4.1K
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...
2.9K
Inhibition of Cdk Activity02:34

Inhibition of Cdk Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
6.2K