Direct cell reprogramming: approaches, mechanisms and progress

The reprogramming of somatic cells with defined factors, which converts cells from one lineage into cells of another, has greatly reshaped our traditional views on cell identity and cell fate determination. Direct reprogramming (also known as transdifferentiation) refers to cell fate conversion with...

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Published in:Nature reviews. Molecular cell biology Vol. 22; no. 6; pp. 410 - 424
Main Authors: Wang, Haofei, Yang, Yuchen, Liu, Jiandong, Qian, Li
Format: Journal Article
Language:English
Published: England Nature Publishing Group 01.06.2021
Subjects:
Animals
Cardiomyocytes
Cell Differentiation - genetics
Cell Differentiation - physiology
Cell fate
Cell Transdifferentiation - genetics
Cell Transdifferentiation - physiology
Cellular Reprogramming - genetics
Cellular Reprogramming - physiology
Epigenesis, Genetic - genetics
Epigenetics
Fibroblasts
Humans
Maturation
Medicine
Metabolism
Molecular modelling
Non-coding RNA
Pluripotency
Somatic cells
Stem cells
Therapeutic applications
Transcription factors
Translation
ISSN:1471-0072, 1471-0080, 1471-0080
Online Access:Get full text
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Summary:The reprogramming of somatic cells with defined factors, which converts cells from one lineage into cells of another, has greatly reshaped our traditional views on cell identity and cell fate determination. Direct reprogramming (also known as transdifferentiation) refers to cell fate conversion without transitioning through an intermediary pluripotent state. Given that the number of cell types that can be generated by direct reprogramming is rapidly increasing, it has become a promising strategy to produce functional cells for therapeutic purposes. This Review discusses the evolution of direct reprogramming from a transcription factor-based method to a small-molecule-driven approach, the recent progress in enhancing reprogrammed cell maturation, and the challenges associated with in vivo direct reprogramming for translational applications. It also describes our current understanding of the molecular mechanisms underlying direct reprogramming, including the role of transcription factors, epigenetic modifications, non-coding RNAs, and the function of metabolic reprogramming, and highlights novel insights gained from single-cell omics studies.
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ISSN:1471-0072
1471-0080
1471-0080
DOI:10.1038/s41580-021-00335-z