Related Experiment Video
Updated: Dec 15, 2025
Using Confocal Analysis of Xenopus laevis to Investigate Modulators of Wnt and Shh Morphogen Gradients
Published on: December 14, 2015
Mapping regulators of cell fate determination: Approaches and challenges
1Department of Bioengineering, University of California, San Diego, La Jolla, California 92093, USA.
Abstract:
Given the limited regenerative capacities of most organs, strategies are needed to efficiently generate large numbers of parenchymal cells capable of integration into the diseased organ. Although it was initially thought that terminally differentiated cells lacked the ability to transdifferentiate, it has since been shown that cellular reprogramming of stromal cells to parenchymal cells through direct lineage conversion holds great potential for the replacement of post-mitotic parenchymal cells lost to disease. To this end, an assortment of genetic, chemical, and mechanical cues have been identified to reprogram cells to different lineages both in vitro and in vivo. However, some key challenges persist that limit broader applications of reprogramming technologies. These include: (1) low reprogramming efficiencies; (2) incomplete functional maturation of derived cells; and (3) difficulty in determining the typically multi-factor combinatorial recipes required for successful transdifferentiation. To improve efficiency by comprehensively identifying factors that regulate cell fate, large scale genetic and chemical screening methods have thus been utilized. Here, we provide an overview of the underlying concept of cell reprogramming as well as the rationale, considerations, and limitations of high throughput screening methods. We next follow with a summary of unique hits that have been identified by high throughput screens to induce reprogramming to various parenchymal lineages. Finally, we discuss future directions of applying this technology toward human disease biology via disease modeling, drug screening, and regenerative medicine.
Insights
Cellular reprogramming can convert stromal cells into parenchymal cells, offering hope for organ repair. High-throughput screening methods are advancing this field to overcome current limitations in efficiency and functional maturation.
Area of Science:
- Cellular and Molecular Biology
- Regenerative Medicine
- Biotechnology
Background:
- Limited organ regeneration necessitates strategies for generating replacement parenchymal cells.
- Direct lineage conversion of stromal cells to parenchymal cells shows promise for replacing cells lost to disease.
- Existing reprogramming methods face challenges including low efficiency, incomplete functional maturation, and difficulty in identifying optimal factor combinations.
Purpose of the Study:
- To provide an overview of cell reprogramming concepts and high-throughput screening (HTS) methods.
- To discuss the rationale, considerations, and limitations of HTS for cell reprogramming.
- To summarize key findings from HTS studies that induce reprogramming to parenchymal lineages.
Main Methods:
- Review of literature on cell reprogramming techniques (genetic, chemical, mechanical cues).
- Analysis of high-throughput screening strategies for identifying reprogramming factors.
- Compilation of identified factors and their impact on inducing transdifferentiation.
Main Results:
- High-throughput screening accelerates the identification of factors regulating cell fate.
- Numerous genetic and chemical factors have been identified to induce reprogramming to various parenchymal lineages.
- These screening methods offer a way to overcome limitations in reprogramming efficiency and factor discovery.
Conclusions:
- High-throughput screening is crucial for advancing cell reprogramming technologies.
- Successful transdifferentiation requires identifying optimal multi-factor combinations.
- Reprogramming holds significant potential for disease modeling, drug screening, and regenerative medicine applications.
More Related Videos
09:29Assessing Cardiomyocyte Subtypes Following Transcription Factor-mediated Reprogramming of Mouse Embryonic Fibroblasts
Published on: March 22, 2017
09:07Prediction and Validation of Gene Regulatory Elements Activated During Retinoic Acid Induced Embryonic Stem Cell Differentiation
Published on: June 21, 2016
Related Concept Videos
01:21Lineage Commitment
02:23Master Transcription Regulators
01:51Determination
01:23Negative Regulator Molecules
01:24Methods of Nuclear Reprogramming
02:33Combinatorial Gene Control
The expression of more than 30,000 genes is controlled by approximately 2000-3000 transcription factors. This is possible because a single transcription factor can recognize more than one regulatory sequence. The specificity in gene...