Human bone marrow harbors cells with neural crest-associated characteristics like human adipose and dermis tissues
Authors: Jacques Foguenne
Gulistan Agirman
Bernard Rogister
Andr√© Gothot
Anil Sharma
Virginie Neirinckx
Fran√ßois Lallemend
Sabine Wislet
C√©cile Coste
Journal: PLoS ONE (2017)
Discipline: Multidisciplinary
Keywords: Neural crest stem-derived cells; regenerative medicine; human bone marrow; gene expression; protein expression
Affiliations: GIGA Neurosciences, University of Li√®ge, Li√®ge, Belgium., Department of Neuroscience, Karolinska Institute, Stockholm, Sweden., GIGA Development, Stem Cells and Regenerative Medicine, University of Li√®ge, Li√®ge, Belgium., Department of Neurology, University of Li√®ge, Li√®ge, Belgium., Department of Laboratory Hematology and Immunology, CHU Li√®ge, Li√®ge, Belgium., Hematology Research Unit, GIGA-I3, University of Li√®ge, Li√®ge, Belgium.

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+ / P75NTR+ / 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. 

Retracted: No

PubPeer comments:
 Figures 6(j) and 6(k) appear to overlap as marked (roughly) in red. 6(i) may also partially overlap. ***  , 
 Reported observation: Figures 6(j) and 6(k) appear to overlap as marked (roughly) in red. 6(i) may also partially overlap. Answer: We verified the images regarding this publication and confirmed the fact that these are 3 different images. As mentioned in the manuscript, we tested the ability of adipose tissue, dermis and bone marrow derived human stem cells to differentiate into chondrocytes. This experiment has been performed several times in 2012 and 2013. Here are some pictures from the lab books of the scientist who performed those experiments. According to those results we confirmed that the data presented in the published manuscript are true data. Taking into consideration that everybody has the right to question data, we only regret that weu2019ve never been contacted regarding this issue, nor by the person who submitted this comment neither by the website mentioning that a comment has been posted regarding one of our study.    , 
 We appreciate the reply, but the fact remains that all 3 panels as published are taken from images of the same field of cells, as can be easily seen by doing overlaps (I left out all 3 overlap to save space).  , 
 #2  According to those results we confirmed that the data presented in the published manuscript are true data. It seems beyond dispute that the visual data presented in the published manuscript are not the images recorded in the lab-book. Perhaps a correction to the paper would help. Actinopolyspora Biskrensis only wants to improve your paper by calling your attention to a minor mistake. , 
 I agree with Actinopolyspora Biskrensis and Salsola Zygophylla that Figure 6 panels i j k appear to all have been derived from the same sample, because they all share an area of overlap. I also agree with Hoya Camphorifolia that the photos provided by the authors are completely different than the figure that is discussed here, which only adds to the concerns I have. Could the authors please do another attempt to find the original photos? , 
 #5 I understand that the authors have found the original photos, and it only remains to replace the incorrect (duplicated) versions that illustrate the paper. , 
 Figure 2F of this paper is also similar to panels in other papers. This paper is part of a set of 5 papers that all appear to contain similar panels. Similar looking panels are shown in red (SOX10), yellow (Nestin) and aqua (p75NTR). The panels might represent the same experiments, but it is strange that they are reused over a period of 6 years. * A. Glejzer et al., Cell. Mol. Life Sci. (2011) 68:2101u20132114. DOI 10.1007 s00018-010-0558-5 * Wislet-Gendebien et al., PLoS ONE 7(10): e46425 (2012). doi:10.1371 journal.pone.0046425 * Neirinckx et al., PLoS ONE 8(5): e64723 (2013). doi: 10.1371 journal.pone.0064723 * Wislet-Gendebien et al., Cellular and Molecular Life Sciences, 69(15):2593-2608 (2012). doi: 10.1007 s00018-012-0937-1 * Coste et al., PLoS ONE 12(7): e0177962 (2017). DOI: 10.1371 journal.pone.0177962 (this paper)    , 
 Supplemental figures: * Marked in green: One of the BMSC panels in Figure S1 (injected adherent stem cells) appears to show an overlap with one of the BMSC panels in Figure S2 (injected spheres).  , 
 See also: https: pubpeer.com publications A4E01599DA3985ADA5851ADE8105A2 u201cThis article has been withdrawn by Sabine Wislet-Gendebien, Cheryl D Souza, Toshitaka Kawarai, Peter St George-Hyslop, David Westaway, Paul Fraser, and Anurag Tandon. The u03b1-synuclein and GAPDH bands at 30 min were superimposed on the earlier time points in Fig. 1B. The GAPDH bands in Fig. 4B were reused in Fig. 7A. u00a9 2020 by The American Society for Biochemistry and Molecular Biology, Inc.u201d , 
 Correction, September 28, 2021: https: journals.plos.org plosone article?id=10.1371 journal.pone.0256484  Following the publication of this article [1] concerns were raised regarding results presented in Figs 1 and 6, S1 and S2 Figs. Specifically, * The SOX10 panel in Fig 1F appears similar to the SOX10 results presented in Fig 2C of [2], the SOX10 results presented in Figure 1D of [3], and the SOX10 results presented in Fig 1E of [4]. * The Fig 6 panels I, J, and K partially overlap with one another, despite being used to represent different experimental conditions. * The Boundary Cap BMSC panel of S1 Fig appears similar to the Boundary Cap BMSC panel of S2 Fig, despite being used to represent different experimental conditions. The authors explained that this study follows up from the results previously described in their Cellular and Molecular Life Sciences and PLOS ONE articles [2, 3, 4], and that the SOX10 panel in Fig 1F represents the same experimental conditions as the SOX10 panels presented in these earlier publications.  Furthermore, the authors explained that the Fig 6I, 6J and 6K panels were wrongly collected from the same human bone marrow sample, as opposed to the cell types mentioned in the figure legend. The authors clarify that the wrong images were inadvertently used during figure preparation and explain that the correct samples were used for the quantification and the preparation of the associated graphs. In the updated figure below, the authors provided the correct panels for the chondrocytic differentiation of bone marrow (panel I), adipose tissue (panel J) and dermis-derived stem cells (panel K). Finally, the authors explained that the Boundary Cap BMSC panels were inadvertently duplicated within S1 and S2 Figs. In addition, the authors pointed out that S1 and S2 Figs were inverted in the original version of the article. The figure originally listed as S1 Fig is updated as S2 Fig. The figure originally listed as S2 Fig has been corrected to replace the duplicate Boundary Cap BMSC panel and is listed as S1 Fig in this correction notice. The originally published, uncorrected version of S2 Fig, updated to S1 Fig in this correction notice, is provided in the S7 File below.  The Board of Ethics and Scientific Integrity of University of Liu00e8ge investigated the overlap between the aforementioned panels and recommended the article be corrected. In addition, a member of PLOS ONEu2019s Editorial Board advised that the updated figures support the results and conclusions reported in the original article. As the original Fig 2C presented in [2] is not licensed for reproduction and distribution under the terms of the Creative Commons Attribution License (or Public Domain License for US gov), this article was republished on September 28, 2021 to remove Fig 1F and replace it with an alternative relevant immunological characterization image. Please download this article again to view the correct version. ,