Evolving principles underlying neural lineage conversion and their relevance for biomedical translation
Lea Jessica Flitsch1, Oliver Brüstle1
1Institute of Reconstructive Neurobiology, University of Bonn School of Medicine & University Hospital Bonn, Bonn, North Rhine Wesphalia, 53127, Germany.
F1000Research
|September 28, 2019
Summary
Recent advances allow purposeful engineering of cell fates, particularly neural cells, by manipulating transcription factors. Understanding epigenetic memory is key for future therapeutic applications in medicine.
Area of Science:
- Developmental Biology
- Stem Cell Biology
- Epigenetics
Background:
- Recent scientific and technological progress has elucidated mechanisms of cell fate acquisition.
- Transcriptional and epigenetic regulation are key during embryonic development.
- This knowledge facilitates in vitro cell fate engineering via transcription factor manipulation.
Purpose of the Study:
- Review the state of the art in cell programming, focusing on neural cell derivation.
- Analyze mechanisms of cell fate changes and epigenetic remodeling in reprogramming and direct conversion.
- Discuss implications of epigenetic memory for disease modeling and neuroregeneration.
Main Methods:
- Literature review of cell programming strategies.
- Analysis of transcriptional and epigenetic regulation in cell fate determination.
- Discussion of implications for biomedical applications.
Main Results:
- Cell fate engineering in vitro is achievable by manipulating lineage-instructing transcription factors.
- Distinct reprogramming and direct conversion strategies vary in their epigenetic remodeling.
- Residual epigenetic memory poses challenges for biomedical applications.
Conclusions:
- Cell programming, especially for neural cells, holds promise for disease modeling and neuroregeneration.
- Further research is needed to address epigenetic memory and translational challenges.
- Cell fate conversion in vivo is an emerging area requiring significant investigation.
Related Concept Videos
Lineage Commitment
4.1K
Commitment is the process whereby stem cells:
4.1K
Forced Transdifferentiation
2.3K
Transdifferentiation, also known as lineage reprogramming, was first discovered by Selman and Kafatos in 1974 in silkmoths. They observed that the moths’ cuticle-producing cells transformed into salt-producing cells. Many such cases of natural transdifferentiation occur in organisms. In humans, pancreatic alpha cells can become beta cells. In newts, the loss of the eye’s lens causes the pigmented epithelial cells to transdifferentiate into the lens cells.
Artificial...
Artificial...
2.3K
Determination
20.8K
During embryogenesis, cells become progressively committed to different fates through a two-step process: specification followed by determination. Specification is demonstrated by removing a segment of an early embryo, “neutrally” culturing the tissue in vitro—for example, in a petri dish with simple medium—and then observing the derivatives. If the cultured region gives rise to cell types that it would normally generate in the embryo, this means that it is specified. In...
20.8K


