Cell Transdifferentiation: A Challenging Strategy with Great Potential.

With the discovery and development of somatic cell nuclear transfer, cell fusion, and induced pluripotent stem cells, cell transdifferentiation research has presented unique advantages and stimulated a heated discussion worldwide. Cell transdifferentiation is a phenomenon by which a cell changes its lineage and acquires the phenotype of other cell types when exposed to certain conditions. Indeed, many adult stem cells and differentiated cells were reported to change their phenotype and transform into other lineages. This article reviews the differentiation of stem cells and classification of transdifferentiation, as well as the advantages, challenges, and prospects of cell transdifferentiation. This review discusses new research directions and the main challenges in the use of transdifferentiation in human cells and molecular replacement therapy. Overall, such knowledge is expected to provide a deep understanding of cell fate and regulation, which can change through differentiation, dedifferentiation, and transdifferentiation, with multiple applications.

[1]  Angela A M Kämpfer,et al.  Investigating nanoplastics toxicity using advanced stem cell-based intestinal and lung in vitro models , 2023, Frontiers in Toxicology.

[2]  Massimiliano Caiazzo,et al.  Induced pluripotent stem cell-derived and directly reprogrammed neurons to study neurodegenerative diseases: The impact of aging signatures , 2022, Frontiers in Aging Neuroscience.

[3]  Henrik Ahlenius,et al.  Past, Present, and Future of Direct Cell Reprogramming. , 2022, Cellular reprogramming.

[4]  M. Heke,et al.  Stem cell-based therapy for human diseases , 2022, Signal Transduction and Targeted Therapy.

[5]  M. Higuchi,et al.  Protocol for isolating adult pituitary stem/progenitor cells in mice , 2022, STAR protocols.

[6]  P. C. Hsieh,et al.  Utility of iPSC-Derived Cells for Disease Modeling, Drug Development, and Cell Therapy , 2022, Cells.

[7]  Y. Jing,et al.  The Emerging Role of Cell Transdifferentiation in Skeletal Development and Diseases , 2022, International journal of molecular sciences.

[8]  C. Verfaillie,et al.  Scalable expansion of iPSC and their derivatives across multiple lineages. , 2022, Reproductive toxicology.

[9]  A. Awidi,et al.  A comparative study of the capability of MSCs isolated from different human tissue sources to differentiate into neuronal stem cells and dopaminergic-like cells , 2022, PeerJ.

[10]  D. Millay Regulation of the myoblast fusion reaction for muscle development, regeneration, and adaptations. , 2022, Experimental cell research.

[11]  M. Qiu,et al.  An efficient method of inducing differentiation of mouse embryonic stem cells into primitive endodermal cells. , 2022, Biochemical and biophysical research communications.

[12]  Bo Peng,et al.  NeuroD1 induces microglial apoptosis and cannot induce microglia-to-neuron cross-lineage reprogramming , 2021, Neuron.

[13]  Y. Shao,et al.  Stem cell-based embryo models: En route to a programmable future. , 2021, Journal of molecular biology.

[14]  Peter Karagiannis,et al.  iPSC-Derived Natural Killer Cells for Cancer Immunotherapy , 2021, Molecules and cells.

[15]  A. Tsiftsoglou Erythropoietin (EPO) as a Key Regulator of Erythropoiesis, Bone Remodeling and Endothelial Transdifferentiation of Multipotent Mesenchymal Stem Cells (MSCs): Implications in Regenerative Medicine , 2021, Cells.

[16]  E. Ghigo,et al.  The Act of Controlling Adult Stem Cell Dynamics: Insights from Animal Models , 2021, Biomolecules.

[17]  M. Kamal,et al.  Neural Stem Cell-Based Therapies and Glioblastoma Management: Current Evidence and Clinical Challenges , 2021, International journal of molecular sciences.

[18]  Yuchen Yang,et al.  Direct cell reprogramming: approaches, mechanisms and progress , 2021, Nature Reviews Molecular Cell Biology.

[19]  A. Khanna,et al.  Sonic hedgehog signals hinder the transcriptional network necessary for pancreatic endoderm formation from human embryonic stem cells , 2021, Genes to cells : devoted to molecular & cellular mechanisms.

[20]  W. Kohrt,et al.  Hematopoietic stem cells produce intermediate lineage adipocyte progenitors that simultaneously express both myeloid and mesenchymal lineage markers in adipose tissue , 2021, Adipocyte.

[21]  A. Llorente,et al.  Adult Stem Cell-Derived Extracellular Vesicles in Cancer Treatment: Opportunities and Challenges , 2020, Cells.

[22]  Huatai Xu,et al.  Glia-to-Neuron Conversion by CRISPR-CasRx Alleviates Symptoms of Neurological Disease in Mice , 2020, Cell.

[23]  B. Barres,et al.  Astrocytic trans-Differentiation Completes a Multicellular Paracrine Feedback Loop Required for Medulloblastoma Tumor Growth , 2020, Cell.

[24]  Ewa Bielczyk-Maczynska White Adipocyte Plasticity in Physiology and Disease , 2019, Cells.

[25]  S. Ferber,et al.  Liver to Pancreas Transdifferentiation , 2019, Current Diabetes Reports.

[26]  F. Gage,et al.  Modeling neuropsychiatric disorders using human induced pluripotent stem cells , 2019, Protein & Cell.

[27]  Michael Xavier Doss,et al.  Current Challenges of iPSC-Based Disease Modeling and Therapeutic Implications , 2019, Cells.

[28]  F. Watt,et al.  Patterning of human epidermal stem cells on undulating elastomer substrates reflects differences in cell stiffness , 2019, Acta biomaterialia.

[29]  G. Dai,et al.  Direct cell reprogramming for tissue engineering and regenerative medicine , 2019, Journal of biological engineering.

[30]  V. Rocha,et al.  Haematopoietic stem cell transplants: principles and indications. , 2019, British journal of hospital medicine.

[31]  H. Ulrich,et al.  Neural stem cell differentiation into mature neurons: Mechanisms of regulation and biotechnological applications. , 2018, Biotechnology advances.

[32]  Y. Yamashita,et al.  Emerging mechanisms of asymmetric stem cell division , 2018, The Journal of cell biology.

[33]  Wei Zhang,et al.  An Insight into the Difficulties in the Discovery of Specific Biomarkers of Limbal Stem Cells , 2018, International journal of molecular sciences.

[34]  H. Clevers,et al.  Defining Adult Stem Cells by Function, not by Phenotype. , 2018, Annual review of biochemistry.

[35]  K. Prasadan,et al.  Endogenous Reprogramming of Alpha Cells into Beta Cells, Induced by Viral Gene Therapy, Reverses Autoimmune Diabetes. , 2018, Cell Stem Cell.

[36]  L. Hui,et al.  Chemical Cocktails Enable Hepatic Reprogramming of Mouse Fibroblasts with a Single Transcription Factor , 2017, Stem cell reports.

[37]  S. Quake,et al.  Converting Adult Pancreatic Islet α Cells into β Cells by Targeting Both Dnmt1 and Arx. , 2017, Cell metabolism.

[38]  T. Komori Cell Death in Chondrocytes, Osteoblasts, and Osteocytes , 2016, International journal of molecular sciences.

[39]  J. Chae,et al.  Comparative Analysis of Human Mesenchymal Stem Cells Derived From Bone Marrow, Placenta, and Adipose Tissue as Sources of Cell Therapy , 2016, Journal of cellular biochemistry.

[40]  B. Cousin,et al.  Immuno-metabolism and adipose tissue: The key role of hematopoietic stem cells. , 2016, Biochimie.

[41]  Y. Tagawa,et al.  Transdifferentiation of mouse visceral yolk sac cells into parietal yolk sac cells in vitro. , 2016, Biochemical and biophysical research communications.

[42]  Kazutoshi Takahashi,et al.  Present and future challenges of induced pluripotent stem cells , 2015, Philosophical Transactions of the Royal Society B: Biological Sciences.

[43]  A. Kahana,et al.  Myocyte Dedifferentiation Drives Extraocular Muscle Regeneration in Adult Zebrafish. , 2015, Investigative ophthalmology & visual science.

[44]  Gideon Rechavi,et al.  Analysing human neural stem cell ontogeny by consecutive isolation of Notch active neural progenitors , 2015, Nature Communications.

[45]  D. Lai,et al.  Pluripotent states of human embryonic stem cells. , 2015, Cellular reprogramming.

[46]  Lei Zhang,et al.  In vivo direct reprogramming of reactive glial cells into functional neurons after brain injury and in an Alzheimer's disease model. , 2014, Cell stem cell.

[47]  J. C. Belmonte,et al.  Regenerative medicine: Transdifferentiation in vivo , 2013, Cell Research.

[48]  M. Lane,et al.  Adipogenesis: from stem cell to adipocyte. , 2012, Annual review of biochemistry.

[49]  Jun S. Song,et al.  Incomplete DNA methylation underlies a transcriptional memory of somatic cells in human iPS cells , 2011, Nature Cell Biology.

[50]  J. I. Izpisúa Belmonte,et al.  Reprogramming with defined factors: from induced pluripotency to induced transdifferentiation. , 2010, Molecular human reproduction.

[51]  L. Bonewald,et al.  Dynamics of the transition from osteoblast to osteocyte , 2010, Annals of the New York Academy of Sciences.

[52]  Thomas Vierbuchen,et al.  Direct conversion of fibroblasts to functional neurons by defined factors , 2010, Nature.

[53]  Jeroen S. van Zon,et al.  Direct cell reprogramming is a stochastic process amenable to acceleration , 2009, Nature.

[54]  Douglas A. Melton,et al.  In vivo reprogramming of adult pancreatic exocrine cells to β-cells , 2008, Nature.

[55]  Shulan Tian,et al.  Induced Pluripotent Stem Cell Lines Derived from Human Somatic Cells , 2007, Science.

[56]  T. Ichisaka,et al.  Induction of Pluripotent Stem Cells from Adult Human Fibroblasts by Defined Factors , 2007, Cell.

[57]  C. Ware,et al.  The FASEB Journal • Research Communication , 2007 .

[58]  S. Yamanaka,et al.  Induction of Pluripotent Stem Cells from Mouse Embryonic and Adult Fibroblast Cultures by Defined Factors , 2006, Cell.

[59]  H. Reichenspurner,et al.  Vascular wall resident progenitor cells: a source for postnatal vasculogenesis , 2006, Development.

[60]  L. Pénicaud,et al.  From heterogeneity to plasticity in adipose tissues: site-specific differences. , 2006, Experimental cell research.

[61]  M. Hedrick,et al.  Fat tissue: an underappreciated source of stem cells for biotechnology. , 2006, Trends in biotechnology.

[62]  M. Fujimoto,et al.  Characterization of multipotent adult stem cells from the skin: transforming growth factor-β (TGF-β) facilitates cell growth , 2004 .

[63]  N. Hashimoto,et al.  Generation of different fates from multipotent muscle stem cells. , 2002, Development.

[64]  A. Sadikot,et al.  Isolation of multipotent adult stem cells from the dermis of mammalian skin , 2001, Nature Cell Biology.

[65]  Perry F. Bartlett,et al.  Purification of a pluripotent neural stem cell from the adult mouse brain , 2001, Nature.

[66]  G. Martin,et al.  Isolation of a pluripotent cell line from early mouse embryos cultured in medium conditioned by teratocarcinoma stem cells. , 1981, Proceedings of the National Academy of Sciences of the United States of America.

[67]  J. Vega,et al.  The osteocyte: a multifunctional cell within the bone. , 2019, Annals of anatomy = Anatomischer Anzeiger : official organ of the Anatomische Gesellschaft.

[68]  Daniel A. De Ugarte,et al.  Multilineage cells from adipose tissue as gene delivery vehicles. , 2003, Human gene therapy.