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Updated: Jan 14, 2026
11:42
Hemogenic Reprogramming of Human Fibroblasts by Enforced Expression of Transcription Factors
Published on: November 4, 2019
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Redefining cellular reprogramming with advanced genomic technologies
Samantha A Morris1,2,3
1Division of Gastroenterology, Hepatology and Endoscopy, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. samorris2@bwh.harvard.edu.
Nature Reviews. Genetics
|October 17, 2025
Summary
Cell reprogramming shows promise for medicine, but challenges like immaturity and low fidelity persist. New genomic and computational tools are revealing how to improve engineered cells for disease modeling and therapy.
Area of Science:
- Cellular reprogramming and regenerative medicine
- Genomic technologies and computational biology
Background:
- Transcription factor-mediated reprogramming (induced pluripotency, directed differentiation) offers potential for disease modeling and regenerative medicine.
- Current reprogramming methods often yield cells with incomplete molecular and functional characteristics, exhibiting immaturity, low fidelity, and heterogeneity.
- These limitations hinder the reliability of engineered cells for disease modeling and therapeutic applications.
Purpose of the Study:
- To explore how recent advances in single-cell genomics and computational frameworks can elucidate mechanisms of reprogramming inefficiency.
- To identify tractable failure points in cell reprogramming processes.
- To guide the design of next-generation reprogramming strategies for improved cell fidelity, maturity, and purity.
Main Methods:
- Utilizing single-cell genomic technologies to analyze cellular heterogeneity and molecular profiles.
- Applying integrative computational frameworks to analyze complex genomic data.
- Employing emerging molecular recording tools to understand reprogramming dynamics.
Main Results:
- Recent technological advances are beginning to reveal the underlying mechanisms of incomplete or inefficient reprogramming.
- Specific failure points in reprogramming protocols have been identified.
- These insights facilitate a deeper understanding of cellular identity manipulation.
Conclusions:
- Advanced genomic and computational tools are crucial for understanding and overcoming reprogramming limitations.
- Mechanism-guided protocol design can lead to stepwise improvements in cell fidelity, maturity, and purity.
- Optimized reprogramming strategies hold the potential to advance engineered cells toward clinical relevance.
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