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Single-cell Atlas Unveils Cellular Heterogeneity and Novel Markers in Human Neonatal and Adult Intervertebral Discs

View ORCID ProfileWensen Jiang, Juliane D. Glaeser, Khosrowdad Salehi, Giselle Kaneda, Pranav Mathkar, Anton Wagner, View ORCID ProfileRitchie Ho, View ORCID ProfileDmitriy Sheyn
doi: https://doi.org/10.1101/2021.10.20.465219
Wensen Jiang
1Orthopaedic Stem Cell Research Laboratory, Cedars-Sinai Medical Center, Los Angeles, California, USA, 90048
2Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA, 90048
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Juliane D. Glaeser
1Orthopaedic Stem Cell Research Laboratory, Cedars-Sinai Medical Center, Los Angeles, California, USA, 90048
2Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA, 90048
5Department of Orthopedics, Cedars-Sinai Medical Center, Los Angeles, California, USA, 90048
6Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, California, USA, 90048
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Khosrowdad Salehi
1Orthopaedic Stem Cell Research Laboratory, Cedars-Sinai Medical Center, Los Angeles, California, USA, 90048
2Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA, 90048
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Giselle Kaneda
1Orthopaedic Stem Cell Research Laboratory, Cedars-Sinai Medical Center, Los Angeles, California, USA, 90048
2Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA, 90048
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Pranav Mathkar
2Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA, 90048
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Anton Wagner
2Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA, 90048
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Ritchie Ho
2Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA, 90048
3Center for Neural Sciences and Medicine, Cedars-Sinai Medical Center, Los Angeles, California, USA, 90048
4Department of Neurology, Cedars-Sinai Medical Center, Los Angeles, California, USA, 90048
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Dmitriy Sheyn
1Orthopaedic Stem Cell Research Laboratory, Cedars-Sinai Medical Center, Los Angeles, California, USA, 90048
2Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA, 90048
5Department of Orthopedics, Cedars-Sinai Medical Center, Los Angeles, California, USA, 90048
6Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, California, USA, 90048
7Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, California, USA, 90048
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  • For correspondence: dmitriy.sheyn@csmc.edu
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SUMMARY

The origin, composition, distribution, and function of cells in the human intervertebral disc (IVD) has not been fully understood. Here, cell atlases of both human neonatal and adult IVDs have been generated and further assessed by gene ontology pathway enrichment, pseudo-time trajectory, histology, and immunofluorescence. Comparison of cell atlases revealed the presence of two sub-populations of notochordal cells (NCs) and their associated markers in both the neonatal and adult IVDs. Developmental trajectories predicted 7 different cell states that describe the developmental process from neonatal to adult cells in IVD and analyzed the NC’s role in the IVD development. A high heterogeneity and gradual transition of annulus fibrosus cells (AFCs) in the neonatal IVD was detected and their potential relevance in IVD development assessed. Collectively, comparing single-cell atlases between neonatal and adult IVDs delineates the landscape of IVD cell biology and may help discovering novel therapeutic targets for IVD degeneration.

Competing Interest Statement

The authors have declared no competing interest.

Footnotes

  • We added two more adult IVD samples and re-analyzed the data, and revised the manuscript accordingly.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Posted November 23, 2021.
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Single-cell Atlas Unveils Cellular Heterogeneity and Novel Markers in Human Neonatal and Adult Intervertebral Discs
Wensen Jiang, Juliane D. Glaeser, Khosrowdad Salehi, Giselle Kaneda, Pranav Mathkar, Anton Wagner, Ritchie Ho, Dmitriy Sheyn
bioRxiv 2021.10.20.465219; doi: https://doi.org/10.1101/2021.10.20.465219
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Single-cell Atlas Unveils Cellular Heterogeneity and Novel Markers in Human Neonatal and Adult Intervertebral Discs
Wensen Jiang, Juliane D. Glaeser, Khosrowdad Salehi, Giselle Kaneda, Pranav Mathkar, Anton Wagner, Ritchie Ho, Dmitriy Sheyn
bioRxiv 2021.10.20.465219; doi: https://doi.org/10.1101/2021.10.20.465219

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