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
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ISSN:1471-0072, 1471-0080, 1471-0080
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Abstract 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.
AbstractList 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.
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.Direct reprogramming converts cells from one lineage into cells of another without going through an intermediary pluripotent state. This Review describes our current understanding of the molecular mechanisms underlying direct reprogramming as well as the progress in improving its efficiency and the maturation of reprogrammed cells, and the challenges associated with its translational applications.
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.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.
Author Qian, Li
Liu, Jiandong
Wang, Haofei
Yang, Yuchen
Author_xml – sequence: 1
  givenname: Haofei
  orcidid: 0000-0001-8914-442X
  surname: Wang
  fullname: Wang, Haofei
  organization: McAllister Heart Institute, University of North Carolina, Chapel Hill, NC, USA
– sequence: 2
  givenname: Yuchen
  surname: Yang
  fullname: Yang, Yuchen
  organization: McAllister Heart Institute, University of North Carolina, Chapel Hill, NC, USA
– sequence: 3
  givenname: Jiandong
  surname: Liu
  fullname: Liu, Jiandong
  organization: McAllister Heart Institute, University of North Carolina, Chapel Hill, NC, USA
– sequence: 4
  givenname: Li
  orcidid: 0000-0001-7614-5618
  surname: Qian
  fullname: Qian, Li
  email: li_qian@med.unc.edu, li_qian@med.unc.edu
  organization: McAllister Heart Institute, University of North Carolina, Chapel Hill, NC, USA. li_qian@med.unc.edu
BackLink https://www.ncbi.nlm.nih.gov/pubmed/33619373$$D View this record in MEDLINE/PubMed
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PublicationTitle Nature reviews. Molecular cell biology
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Snippet The reprogramming of somatic cells with defined factors, which converts cells from one lineage into cells of another, has greatly reshaped our traditional...
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SubjectTerms 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
Title Direct cell reprogramming: approaches, mechanisms and progress
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