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

doi:10.1016/j.isci.2022.104504

Single-cell atlas unveils cellular heterogeneity and novel markers in human neonatal and adult intervertebral discs

iScience. 2022 Jun 2;25(7):104504. doi: 10.1016/j.isci.2022.104504. eCollection 2022 Jul 15.

Authors

Wensen Jiang^{1

2}, Juliane D Glaeser^{1

2

3

4}, Khosrowdad Salehi^{1

2}, Giselle Kaneda^{1

2}, Pranav Mathkar², Anton Wagner², Ritchie Ho^{2

5

6

7}, Dmitriy Sheyn^{1

2

3

4

7}

Affiliations

¹ Orthopaedic Stem Cell Research Laboratory, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
² Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
³ Department of Orthopedics, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
⁴ Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
⁵ Center for Neural Sciences and Medicine, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
⁶ Department of Neurology, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
⁷ Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.

Abstract

The origin, composition, distribution, and function of cells in the human intervertebral disc (IVD) have 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 subpopulations 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 discover novel therapeutic targets for IVD degeneration.

Keywords: complex system biology; developmental biology; transcriptomics.

Grants and funding

K01 AR071512/AR/NIAMS NIH HHS/United States