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Persistence of FoxJ1+ Pax6+ Sox2+ ependymal cells throughout life in the human spinal cord

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Abstract

Ependymal cells lining the central canal of the spinal cord play a crucial role in providing a physical barrier and in the circulation of cerebrospinal fluid. These cells express the FOXJ1 and SOX2 transcription factors in mice and are derived from various neural tube populations, including embryonic roof and floor plate cells. They exhibit a dorsal–ventral expression pattern of spinal cord developmental transcription factors (such as MSX1, PAX6, ARX, and FOXA2), resembling an embryonic-like organization. Although this ependymal region is present in young humans, it appears to be lost with age. To re-examine this issue, we collected 17 fresh spinal cords from organ donors aged 37–83 years and performed immunohistochemistry on lightly fixed tissues. We observed cells expressing FOXJ1 in the central region in all cases, which co-expressed SOX2 and PAX6 as well as RFX2 and ARL13B, two proteins involved in ciliogenesis and cilia-mediated sonic hedgehog signaling, respectively. Half of the cases exhibited a lumen and some presented portions of the spinal cord with closed and open central canals. Co-staining of FOXJ1 with other neurodevelopmental transcription factors (ARX, FOXA2, MSX1) and NESTIN revealed heterogeneity of the ependymal cells. Interestingly, three donors aged > 75 years exhibited a fetal-like regionalization of neurodevelopmental transcription factors, with dorsal and ventral ependymal cells expressing MSX1, ARX, and FOXA2. These results provide new evidence for the persistence of ependymal cells expressing neurodevelopmental genes throughout human life and highlight the importance of further investigation of these cells.

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Acknowledgements

We thank the French Agency of biomedicine and all Montpellier Biocampus facilities for help (RHEM, MRI) and excellent technical work. We also warmly thank all organ donors and their family as well as nurses and all medical staff from the Unit of Donation and Transplantation (Montpellier hospital). We thank Dr Ariel Levine (NIH, USA) for permission to use screen capture from the Human Spinal Cord snRNAseq Viewer (https://vmenon.shinyapps.io/humanspinalcord/)

Funding

This work was supported by grants from IRP (Switzerland, 2013), IRME (France, 2020), AFM (France, 2019), ANR ERANET Neuroniche (JP Hugnot, 2019), ARSEP (France, 2020). T Chevreau was supported by an AFM PhD fellowship.

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  1. Luc Bauchet and Jean-Philippe Hugnot contributed equally.

Authors and Affiliations

  1. Institut de Génomique Fonctionnelle, Université de Montpellier, CNRS, INSERM, 141 rue de la Cardonille, 34091, Montpellier, France

    Chantal Ripoll, Robert Chevreau, Luc Bauchet & Jean-Philippe Hugnot

  2. Neurosurgery Department, CHU Montpellier, Montpellier, France

    Gaetan Poulen, Nicolas Lonjon & Luc Bauchet

  3. Department of Donation and Transplantation, Coordination Unit, CHU Montpellier, Montpellier, France

    Florence Vachiery-Lahaye

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  1. Chantal Ripoll
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  2. Gaetan Poulen
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Contributions

All authors contributed to the study conception and design. Spinal cords were mainly extracted and collected by LB, RC, NL and GP. Chantal Ripoll designed and performed histology, quantifications and figure preparation. RC participated in histology, performed data analysis and quantifications. FV-L coordinated informed consents and spinal cord collections. The first draft of the manuscript was written by JPH and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.”

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Correspondence to Jean-Philippe Hugnot.

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The authors have no relevant financial or non-financial interests to disclose.

Ethical approval

This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted to Dr Luc Bauchet by the French “Agence de la biomédecine”, n° SPGED19-3-4692, April, 2nd, 2019.

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Informed consent was obtained from relatives of organ donors included in the study.

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Ripoll, C., Poulen, G., Chevreau, R. et al. Persistence of FoxJ1+ Pax6+ Sox2+ ependymal cells throughout life in the human spinal cord. Cell. Mol. Life Sci. 80, 181 (2023). https://doi.org/10.1007/s00018-023-04811-x

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