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Front Mol Neurosci
2019 Feb 22;12:39. doi: 10.3389/fnmol.2019.00039.
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Human Pluripotent Stem Cell-Derived Neural Crest Cells for Tissue Regeneration and Disease Modeling.
Srinivasan A
,
Toh YC
.
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Neural crest cells (NCCs) are a multipotent and migratory cell population in the developing embryo that contribute to the formation of a wide range of tissues. Defects in the development, differentiation and migration of NCCs give rise to a class of syndromes and diseases that are known as neurocristopathies. NCC development has historically been studied in a variety of animal models, including xenopus, chick and mouse. In the recent years, there have been efforts to study NCC development and disease in human specific models, with protocols being established to derive NCCs from human pluripotent stem cells (hPSCs), and to further differentiate these NCCs to neural, mesenchymal and other lineages. These in vitro differentiation platforms are a valuable tool to gain a better understanding of the molecular mechanisms involved in human neural crest development. The use of induced pluripotent stem cells (iPSCs) derived from patients afflicted with neurocristopathies has also enabled the study of defective human NCC development using these in vitro platforms. Here, we review the various in vitro strategies that have been used to derive NCCs from hPSCs and to specify NCCs into cranial, trunk, and vagal subpopulations and their derivatives. We will also discuss the potential applications of these human specific NCC platforms, including the use of iPSCs for disease modeling and the potential of NCCs for future regenerative applications.
FIGURE 1. Overview of in vivo NCC development and derivatives and in vitro derivation of human NCCs and major applications. (A) During gastrulation, the neural plate border is specified by BMP, WNT, FGF, and Notch/Delta signaling from the surrounding neural plate, non-neural ectoderm and mesoderm. NCCs are specified at the neural plate border region and then reside in the dorsal portion of the neural tube. Following neural tube closure, they undergo an epithelial-mesenchymal transition and migrate along the anterior-posterior axis of the embryo to give rise to different derivatives based on the region (cranial, cardiac, vagal, or trunk) (Milet and Monsoro-Burq, 2012b; Simoes-Costa and Bronner, 2015; Gandhi and Bronner, 2018). (B) The major approaches by which human NCCs are derived in vitro from hPSCs and differentiated to selected derivatives. The potential applications of these derivatives in regenerative medicine and disease modeling.
Achilleos,
Neural crest stem cells: discovery, properties and potential for therapy.
2012, Pubmed
Achilleos,
Neural crest stem cells: discovery, properties and potential for therapy.
2012,
Pubmed
Amiel,
Hirschsprung disease, associated syndromes and genetics: a review.
2008,
Pubmed
Bajpai,
CHD7 cooperates with PBAF to control multipotent neural crest formation.
2010,
Pubmed
,
Xenbase
Betters,
Analysis of early human neural crest development.
2010,
Pubmed
Brokhman,
Peripheral sensory neurons differentiate from neural precursors derived from human embryonic stem cells.
2008,
Pubmed
Chambers,
Highly efficient neural conversion of human ES and iPS cells by dual inhibition of SMAD signaling.
2009,
Pubmed
Chijimatsu,
Characterization of Mesenchymal Stem Cell-Like Cells Derived From Human iPSCs via Neural Crest Development and Their Application for Osteochondral Repair.
2017,
Pubmed
Du,
Quantitative Multimodal Evaluation of Passaging Human Neural Crest Stem Cells for Peripheral Nerve Regeneration.
2018,
Pubmed
Fattahi,
Deriving human ENS lineages for cell therapy and drug discovery in Hirschsprung disease.
2016,
Pubmed
Gandhi,
Insights into neural crest development from studies of avian embryos.
2018,
Pubmed
Hackland,
Top-Down Inhibition of BMP Signaling Enables Robust Induction of hPSCs Into Neural Crest in Fully Defined, Xeno-free Conditions.
2017,
Pubmed
Huang,
Generating trunk neural crest from human pluripotent stem cells.
2016,
Pubmed
Iwashita,
Hirschsprung disease is linked to defects in neural crest stem cell function.
2003,
Pubmed
Jiang,
Isolation and characterization of neural crest stem cells derived from in vitro-differentiated human embryonic stem cells.
2009,
Pubmed
Jiao,
Differentiation defect in neural crest-derived smooth muscle cells in patients with aortopathy associated with bicuspid aortic valves.
2016,
Pubmed
Jones,
Regenerative effects of human embryonic stem cell-derived neural crest cells for treatment of peripheral nerve injury.
2018,
Pubmed
Kim,
Generation of multipotent induced neural crest by direct reprogramming of human postnatal fibroblasts with a single transcription factor.
2014,
Pubmed
Kimura,
Stem cells purified from human induced pluripotent stem cell-derived neural crest-like cells promote peripheral nerve regeneration.
2018,
Pubmed
Lai,
Correction of Hirschsprung-Associated Mutations in Human Induced Pluripotent Stem Cells Via Clustered Regularly Interspaced Short Palindromic Repeats/Cas9, Restores Neural Crest Cell Function.
2017,
Pubmed
Le Douarin,
Multipotentiality of the neural crest.
2003,
Pubmed
Le Douarin,
Neural crest cell plasticity and its limits.
2004,
Pubmed
Lee,
Isolation and directed differentiation of neural crest stem cells derived from human embryonic stem cells.
2007,
Pubmed
Lee,
Modelling pathogenesis and treatment of familial dysautonomia using patient-specific iPSCs.
2009,
Pubmed
Lee,
Derivation of neural crest cells from human pluripotent stem cells.
2010,
Pubmed
Li,
Characterization and transplantation of enteric neural crest cells from human induced pluripotent stem cells.
2018,
Pubmed
Menendez,
Wnt signaling and a Smad pathway blockade direct the differentiation of human pluripotent stem cells to multipotent neural crest cells.
2011,
Pubmed
Menendez,
Directed differentiation of human pluripotent cells to neural crest stem cells.
2013,
Pubmed
Mica,
Modeling neural crest induction, melanocyte specification, and disease-related pigmentation defects in hESCs and patient-specific iPSCs.
2013,
Pubmed
Milet,
Neural crest induction at the neural plate border in vertebrates.
2012,
Pubmed
,
Xenbase
Milet,
Embryonic stem cell strategies to explore neural crest development in human embryos.
2012,
Pubmed
Mimura,
Bone morphogenetic protein 4 promotes craniofacial neural crest induction from human pluripotent stem cells.
2016,
Pubmed
Okuno,
CHARGE syndrome modeling using patient-iPSCs reveals defective migration of neural crest cells harboring CHD7 mutations.
2017,
Pubmed
Paulussen,
Ewing tumour: incidence, prognosis and treatment options.
2001,
Pubmed
Pla,
The neural border: Induction, specification and maturation of the territory that generates neural crest cells.
2018,
Pubmed
,
Xenbase
Pomp,
Generation of peripheral sensory and sympathetic neurons and neural crest cells from human embryonic stem cells.
2005,
Pubmed
Rogers,
Neural crest specification: tissues, signals, and transcription factors.
2012,
Pubmed
Saito,
The dorsal aorta initiates a molecular cascade that instructs sympatho-adrenal specification.
2012,
Pubmed
Sanlaville,
CHARGE syndrome: an update.
2007,
Pubmed
Schlieve,
Neural Crest Cell Implantation Restores Enteric Nervous System Function and Alters the Gastrointestinal Transcriptome in Human Tissue-Engineered Small Intestine.
2017,
Pubmed
Simões-Costa,
Establishing neural crest identity: a gene regulatory recipe.
2015,
Pubmed
Slaugenhaupt,
Tissue-specific expression of a splicing mutation in the IKBKAP gene causes familial dysautonomia.
2001,
Pubmed
Srinivasan,
Substrate stiffness modulates the multipotency of human neural crest derived ectomesenchymal stem cells via CD44 mediated PDGFR signaling.
2018,
Pubmed
Stuhlmiller,
Current perspectives of the signaling pathways directing neural crest induction.
2012,
Pubmed
,
Xenbase
Tollemar,
Stem cells, growth factors and scaffolds in craniofacial regenerative medicine.
2016,
Pubmed
Tseng,
Substrate-mediated reprogramming of human fibroblasts into neural crest stem-like cells and their applications in neural repair.
2016,
Pubmed
Tu,
The Histogenesis of Ewing Sarcoma.
2017,
Pubmed
Walsh,
Practical considerations concerning the use of stem cells for peripheral nerve repair.
2009,
Pubmed
Wang,
Induced pluripotent stem cells for neural tissue engineering.
2011,
Pubmed
Workman,
Engineered human pluripotent-stem-cell-derived intestinal tissues with a functional enteric nervous system.
2017,
Pubmed
Xu,
Human iPSC-derived neural crest stem cells promote tendon repair in a rat patellar tendon window defect model.
2013,
Pubmed
von Levetzow,
Modeling initiation of Ewing sarcoma in human neural crest cells.
2011,
Pubmed
