Academic Journal

Redefining cellular reprogramming with advanced genomic technologies.

Bibliographic Details
Title: Redefining cellular reprogramming with advanced genomic technologies.
Authors: Morris SA; Division of Gastroenterology, Hepatology and Endoscopy, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. samorris2@bwh.harvard.edu.; Division of Genetics, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. samorris2@bwh.harvard.edu.; Department of Systems Biology, Harvard Medical School, Boston, MA, USA. samorris2@bwh.harvard.edu.
Source: Nature reviews. Genetics [Nat Rev Genet] 2026 Mar; Vol. 27 (3), pp. 193-211. Date of Electronic Publication: 2025 Oct 17.
Publication Type: Journal Article; Review
Language: English
Journal Info: Publisher: Nature Pub. Group Country of Publication: England NLM ID: 100962779 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1471-0064 (Electronic) Linking ISSN: 14710056 NLM ISO Abbreviation: Nat Rev Genet Subsets: MEDLINE
Imprint Name(s): Original Publication: London, UK : Nature Pub. Group, [2000-
MeSH Terms: Cellular Reprogramming*/genetics , Genomics*/methods , Cellular Reprogramming Techniques*/methods, Induced Pluripotent Stem Cells/cytology ; Induced Pluripotent Stem Cells/metabolism ; Cell Differentiation/genetics ; Regenerative Medicine/methods ; Humans ; Animals ; Single-Cell Analysis
Abstract: Manipulating cell identity through transcription factor-mediated reprogramming, induced pluripotency or directed differentiation holds promise for disease modelling and regenerative medicine. Yet the cells produced by these methods often do not fully recapitulate the molecular and functional characteristics of their native counterparts. Immaturity, low fidelity and heterogeneity remain barriers, limiting reliability for modelling human disease and therapeutic use. Recent advances in single-cell genomic technologies, integrative computational frameworks and emerging molecular recording tools are beginning to reveal the mechanisms underlying incomplete or inefficient reprogramming and highlight tractable failure points. Together, these approaches could support mechanism-guided protocol design and stepwise gains in fidelity, maturity and purity, potentially moving engineered cells towards clinical relevance and informing design principles for next-generation reprogramming strategies.
(© 2025. Springer Nature Limited.)
Competing Interests: Competing interests: S.A.M. cofounded and has a financial interest in CapyBio Inc, a company investigating novel processes for reprogramming cells. S.A.M’s interests were reviewed and are managed by Brigham and Women’s Hospital and Mass General Brigham in accordance with their conflict-of-interest policies.
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Grant Information: R01 DK139580 United States DK NIDDK NIH HHS; R01 GM126112 United States GM NIGMS NIH HHS; R35 GM153468 United States GM NIGMS NIH HHS
Entry Date(s): Date Created: 20251017 Date Completed: 20260220 Latest Revision: 20260220
Update Code: 20260220
PubMed Central ID: PMC12785792
DOI: 10.1038/s41576-025-00899-y
PMID: 41107536
Database: MEDLINE
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