Related Experiment Video
Updated: Jul 12, 2025
11:00
Reprogramming Mouse Embryonic Fibroblasts with Transcription Factors to Induce a Hemogenic Program
Published on: December 16, 2016
7.3K
Deciphering the decisive factors driving fate bifurcations in somatic cell reprogramming.
Chunshen Long1, Hanshuang Li1, Pengfei Liang1
1State Key Laboratory of Reproductive Regulation and Breeding of Grassland Livestock, Institutes of Biomedical Sciences, School of Life Sciences, Inner Mongolia University, Hohhot 010070, China.
Molecular Therapy. Nucleic Acids
|October 23, 2023
Summary
Somatic cell reprogramming involves continuous cell fate transitions. This study identifies key factors driving induced pluripotent stem cells (iPSCs) towards stromal-like cells (SLCs) or trophoblast-like cells (TLCs) to improve reprogramming efficiency.
Area of Science:
- Stem Cell Biology
- Epigenetics
- Developmental Biology
Background:
- Somatic cell reprogramming is a dynamic process with intermediates facing molecular bottlenecks.
- Understanding cell fate decisions is crucial for efficient reprogramming to pluripotency.
- Previous studies highlight the mesenchymal-epithelial transition and pluripotency network activation.
Purpose of the Study:
- To identify decisive factors governing cell fate bifurcations during induced pluripotent stem cell (iPSC) reprogramming.
- To elucidate the molecular drivers leading to stromal-like cells (SLCs) versus trophoblast-like cells (TLCs) differentiation.
- To provide insights for enhancing reprogramming efficiency by manipulating cell fate trajectories.
Main Methods:
- Reconstruction of cellular trajectories to identify iPSCs/SLCs and iPSCs/TLCs fate bifurcations.
- Analysis of gene regulatory networks to pinpoint key transcription factors.
- Comparative analysis of gene expression patterns associated with different cell fates.
Main Results:
- Successful reprogramming involves mesenchymal-epithelial transition and pluripotency network activation.
- iPSC/SLC fate is linked to cell cycle inhibition and extracellular matrix gene activation.
- iPSC/TLC fate is characterized by up-regulation of placenta development genes.
- Seven factors (e.g., Taf7, Ezh2, Klf2) drive iPSCs/SLCs reprogramming, while three (e.g., Cdc5l, Klf4, Nanog) drive iPSCs/TLCs bifurcation.
- Eleven factors (e.g., Cebpb, Sox4, Junb) promote SLC fate, and four factors (e.g., Gata2, Jund, Ctnnb1) promote TLC fate.
Conclusions:
- Specific gene regulatory networks and key factors dictate cell fate decisions during reprogramming.
- Identifying these drivers offers a strategy to avoid alternative fates and improve reprogramming outcomes.
- This research deepens the understanding of cell fate determination in the context of induced pluripotency.
Related Concept Videos
01:29Somatic to iPS Cell Reprogramming
2.2K
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...
2.2K
01:24Methods of Nuclear Reprogramming
1.8K
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...
1.8K
01:14Introduction to Nuclear Reprogramming
1.9K
Nuclear reprogramming is the process of switching gene expression of one cell type to that of another cell type, usually from a differentiated cell state to an undifferentiated cell state. Differentiation occurs during processes such as development and morphogenesis, tissue regeneration, and malignancy. Cells can also be artificially induced to reprogram their gene expression by techniques such as nuclear transfer, induced pluripotency, and cell fusion. Such techniques have many applications in...
1.9K
01:21Lineage Commitment
3.0K
Commitment is the process whereby stem cells:
3.0K
01:27Molecular Factors Affecting Cell Division
3.1K
Several external and internal factors influence the initiation and inhibition of cell division. For instance, the death of nearby cells or the release of human growth hormone (hGH) promotes cell division. In contrast, lack of hGH or crowding of cells can inhibit cell division.
Several proteins function as internal regulators to ensure each cell cycle stage is completed faithfully before proceeding to the next. Regulator molecules may act directly or influence the activity or production of other...
Several proteins function as internal regulators to ensure each cell cycle stage is completed faithfully before proceeding to the next. Regulator molecules may act directly or influence the activity or production of other...
3.1K
01:06Induced Pluripotent Stem Cells
4.1K
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...
Somatic...
4.1K