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      Human bone marrow harbors cells with neural crest-associated characteristics like human adipose and dermis tissues

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          Abstract

          Adult neural crest stem-derived cells (NCSC) are of extraordinary high plasticity and promising candidates for use in regenerative medicine. Several locations such as skin, adipose tissue, dental pulp or bone marrow have been described in rodent, as sources of NCSC. However, very little information is available concerning their correspondence in human tissues, and more precisely for human bone marrow. The main objective of this study was therefore to characterize NCSC from adult human bone marrow. In this purpose, we compared human bone marrow stromal cells to human adipose tissue and dermis, already described for containing NCSC. We performed comparative analyses in terms of gene and protein expression as well as functional characterizations. It appeared that human bone marrow, similarly to adipose tissue and dermis, contains NESTIN + / SOX9 + / TWIST + / SLUG + / P75 NTR+ / BRN3A +/ MSI1 +/ SNAIL1 + cells and were able to differentiate into melanocytes, Schwann cells and neurons. Moreover, when injected into chicken embryos, all those cells were able to migrate and follow endogenous neural crest migration pathways. Altogether, the phenotypic characterization and migration abilities strongly suggest the presence of neural crest-derived cells in human adult bone marrow.

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          Most cited references55

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          Fate of the mammalian cardiac neural crest.

          A subpopulation of neural crest termed the cardiac neural crest is required in avian embryos to initiate reorganization of the outflow tract of the developing cardiovascular system. In mammalian embryos, it has not been previously experimentally possible to study the long-term fate of this population, although there is strong inference that a similar population exists and is perturbed in a number of genetic and teratogenic contexts. We have employed a two-component genetic system based on Cre/lox recombination to label indelibly the entire mouse neural crest population at the time of its formation, and to detect it at any time thereafter. Labeled cells are detected throughout gestation and in postnatal stages in major tissues that are known or predicted to be derived from neural crest. Labeling is highly specific and highly efficient. In the region of the heart, neural-crest-derived cells surround the pharyngeal arch arteries from the time of their formation and undergo an altered distribution coincident with the reorganization of these vessels. Labeled cells populate the aorticopulmonary septum and conotruncal cushions prior to and during overt septation of the outflow tract, and surround the thymus and thyroid as these organs form. Neural-crest-derived mesenchymal cells are abundantly distributed in midgestation (E9.5-12.5), and adult derivatives of the third, fourth and sixth pharyngeal arch arteries retain a substantial contribution of labeled cells. However, the population of neural-crest-derived cells that infiltrates the conotruncus and which surrounds the noncardiac pharyngeal organs is either overgrown or selectively eliminated as development proceeds, resulting for these tissues in a modest to marginal contribution in late fetal and postnatal life.
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            Epithelial-mesenchymal signalling regulating tooth morphogenesis.

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              Isolation and characterization of multipotent skin-derived precursors from human skin.

              We have previously isolated, expanded, and characterized a multipotent precursor cell from mammalian dermis (termed skin-derived precursors [SKPs]) that can differentiate into both neural and mesodermal progeny. In this study, we report the isolation, expansion, and characterization of a similar precursor cell from neonatal human foreskin tissue. Like their rodent counterparts, human SKPs grew in suspension as spheres in the presence of the mitogens fibroblast growth factor 2 and epidermal growth factor and expressed nestin, fibronectin, vimentin, and characteristic embryonic transcription factors. Human SKPs could be maintained in culture for long periods of time and would still differentiate into neurons, glia, and smooth muscle cells, including cells with the phenotype of peripheral neurons and Schwann cells. Clonal analysis indicated that single SKP cells were multipotent and could give rise to all of these progeny. Moreover, human SKPs apparently derive from an endogenous precursor within human foreskin; a subpopulation of dissociated primary foreskin cells could differentiate into neurons, a cell type never seen in skin, and the initial spheres to develop from skin expressed the same markers and had the same potential as do passaged SKPs. Together, these data indicate that SKPs are an endogenous multipotent precursor cell present in human skin that can be isolated and expanded and differentiate into both neural and mesodermal cell types.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                6 July 2017
                2017
                : 12
                : 7
                : e0177962
                Affiliations
                [1 ]GIGA Neurosciences, University of Liège, Liège, Belgium
                [2 ]Department of Neuroscience, Karolinska Institute, Stockholm, Sweden
                [3 ]GIGA Development, Stem Cells and Regenerative Medicine, University of Liège, Liège, Belgium
                [4 ]Department of Neurology, University of Liège, Liège, Belgium
                [5 ]Department of Laboratory Hematology and Immunology, CHU Liège, Liège, Belgium
                [6 ]Hematology Research Unit, GIGA-I3, University of Liège, Liège, Belgium
                Instituto Butantan, BRAZIL
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                • Conceptualization: SW AG.

                • Formal analysis: CC VN AS AG JF FL.

                • Funding acquisition: AG SW FL.

                • Investigation: CC VN AS.

                • Methodology: SW JF AG.

                • Project administration: FL BR AG SW.

                • Resources: BR FL SW AG.

                • Software: JF.

                • Supervision: FL BR AG SW.

                • Visualization: CC VN AS GA BR JF FL AG SW.

                • Writing – original draft: CC AG SW.

                • Writing – review & editing: CC AG SW.

                Article
                PONE-D-16-45740
                10.1371/journal.pone.0177962
                5500284
                28683107
                0721d4f3-aa1e-4163-a4cc-5db0901a1f11
                © 2017 Coste et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 23 December 2016
                : 5 May 2017
                Page count
                Figures: 13, Tables: 2, Pages: 26
                Funding
                Funded by: funder-id http://dx.doi.org/10.13039/501100002661, Fonds De La Recherche Scientifique - FNRS;
                Award ID: TELEVIE 7.4523.14
                Award Recipient :
                Funded by: funder-id http://dx.doi.org/10.13039/501100002661, Fonds De La Recherche Scientifique - FNRS;
                Award ID: J.0067.16 – CDR
                Award Recipient :
                Funded by: Fond Léon Frédéricq
                Award Recipient :
                Funded by: Fonds Spéciaux ULg
                Award Recipient :
                This work was supported by a grant from the Télévie - Fonds National de la Recherche Scientifique (FNRS) of Belgium, by a grant of the Fonds Spéciaux of the University of Liège, Belgium, and by a grant of Leon Fredericq Foundation. François Lallemend is supported by the Swedish Medical Research Council, Karolinska Institute, Ragnar Söderberg foundation, Knut and Alice Wallenberg Foundation, Åke Wiberg foundation and the Swedish Brain Foundation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Biology and Life Sciences
                Cell Biology
                Cellular Types
                Animal Cells
                Bone Marrow Cells
                Biology and Life Sciences
                Anatomy
                Biological Tissue
                Adipose Tissue
                Medicine and Health Sciences
                Anatomy
                Biological Tissue
                Adipose Tissue
                People and Places
                Population Groupings
                Age Groups
                Adults
                Biology and Life Sciences
                Developmental Biology
                Cell Differentiation
                Biology and Life Sciences
                Developmental Biology
                Embryology
                Embryos
                Biology and Life Sciences
                Biochemistry
                Proteins
                Cytoskeletal Proteins
                Nestin
                Biology and Life Sciences
                Cell Biology
                Cellular Types
                Animal Cells
                Stem Cells
                Mesenchymal Stem Cells
                Biology and Life Sciences
                Developmental Biology
                Cell Differentiation
                Neuronal Differentiation
                Custom metadata
                All relevant data are within the paper and its Supporting Information files.

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