An ependymal cell census identifies heterogeneous and ongoing cell maturation in the adult mouse spinal cord that changes dynamically on injury

Aida Rodrigo Albors; Gail A. Singer; Enric Llorens-Bobadilla; Jonas Frisén; Andrew P. May; Chris P. Ponting; Kate G. Storey

doi:10.1016/j.devcel.2023.01.003

An ependymal cell census identifies heterogeneous and ongoing cell maturation in the adult mouse spinal cord that changes dynamically on injury

Aida Rodrigo Albors, Gail A. Singer, Enric Llorens-Bobadilla, Jonas Frisén, Andrew P. May, Chris P. Ponting, Kate G. Storey (Lead / Corresponding author)

Research output: Contribution to journal › Article › peer-review

11 Citations (Scopus)

107 Downloads (Pure)

Abstract

The adult spinal cord stem cell potential resides within the ependymal cell population and declines with age. Ependymal cells are, however, heterogeneous, and the biological diversity this represents and how it changes with age remain unknown. Here, we present a single-cell transcriptomic census of spinal cord ependymal cells from adult and aged mice, identifying not only all known ependymal cell subtypes but also immature as well as mature cell states. By comparing transcriptomes of spinal cord and brain ependymal cells, which lack stem cell abilities, we identify immature cells as potential spinal cord stem cells. Following spinal cord injury, these cells re-enter the cell cycle, which is accompanied by a short-lived reversal of ependymal cell maturation. We further analyze ependymal cells in the human spinal cord and identify widespread cell maturation and altered cell identities. This in-depth characterization of spinal cord ependymal cells provides insight into their biology and informs strategies for spinal cord repair.

Original language	English
Pages (from-to)	239-255.e10
Number of pages	17
Journal	Developmental Cell
Volume	58
Issue number	3
Early online date	26 Jan 2023
DOIs	https://doi.org/10.1016/j.devcel.2023.01.003
Publication status	Published - 6 Feb 2023

Keywords

ependymal cell
spinal cord
spinal cord injury
cell maturation
adult neural stem cell
mouse
human
scRNA-seq

ASJC Scopus subject areas

General Biochemistry,Genetics and Molecular Biology
Molecular Biology
Cell Biology
Developmental Biology

Access to Document

10.1016/j.devcel.2023.01.003Licence: CC BY-NC-ND

Final published versionFinal published version, 7.94 MBLicence: CC BY-NC-ND

Cite this

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title = "An ependymal cell census identifies heterogeneous and ongoing cell maturation in the adult mouse spinal cord that changes dynamically on injury",

abstract = "The adult spinal cord stem cell potential resides within the ependymal cell population and declines with age. Ependymal cells are, however, heterogeneous, and the biological diversity this represents and how it changes with age remain unknown. Here, we present a single-cell transcriptomic census of spinal cord ependymal cells from adult and aged mice, identifying not only all known ependymal cell subtypes but also immature as well as mature cell states. By comparing transcriptomes of spinal cord and brain ependymal cells, which lack stem cell abilities, we identify immature cells as potential spinal cord stem cells. Following spinal cord injury, these cells re-enter the cell cycle, which is accompanied by a short-lived reversal of ependymal cell maturation. We further analyze ependymal cells in the human spinal cord and identify widespread cell maturation and altered cell identities. This in-depth characterization of spinal cord ependymal cells provides insight into their biology and informs strategies for spinal cord repair.",

keywords = "ependymal cell, spinal cord, spinal cord injury, cell maturation, adult neural stem cell, mouse, human, scRNA-seq",

author = "{Rodrigo Albors}, Aida and Singer, {Gail A.} and Enric Llorens-Bobadilla and Jonas Fris{\'e}n and May, {Andrew P.} and Ponting, {Chris P.} and Storey, {Kate G.}",

note = "Funding Information: This project was supported by the Wellcome Trust (Wellcome Investigator award WT102817AIA to K.G.S.) and a Wings for Life grant (WFL-UK-24/17 Proj 171) to K.G.S. This project and A.R.A. were also supported by the European Union's Horizon 2020 Marie Sk{\l}odowska-Curie grant agreement no. 753812. A.R.A. was also supported by the Wellcome ISSF COVID-19 Research Momentum fund (119293) and the University of Dundee. G.A.S. was supported by Wings for Life. C.P.P. was supported by the MRC (MC_UU_00007/15). A.P.M. was supported by the Chan Zuckerberg Biohub. E.L.-B. and J.F. were supported by the Swedish Research Council, Knut and Alice Wallenbergs Stiftelse, and the Swedish Cancer Foundation. The confocal microscope used for imaging was purchased with support from Wellcome Trust Multi-User Equipment grant (WT101468). Copyright: {\textcopyright} 2023 The Author(s). Published by Elsevier Inc. All rights reserved.",

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doi = "10.1016/j.devcel.2023.01.003",

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T1 - An ependymal cell census identifies heterogeneous and ongoing cell maturation in the adult mouse spinal cord that changes dynamically on injury

AU - Rodrigo Albors, Aida

AU - Singer, Gail A.

AU - Llorens-Bobadilla, Enric

AU - Frisén, Jonas

AU - May, Andrew P.

AU - Ponting, Chris P.

AU - Storey, Kate G.

N1 - Funding Information: This project was supported by the Wellcome Trust (Wellcome Investigator award WT102817AIA to K.G.S.) and a Wings for Life grant (WFL-UK-24/17 Proj 171) to K.G.S. This project and A.R.A. were also supported by the European Union's Horizon 2020 Marie Skłodowska-Curie grant agreement no. 753812. A.R.A. was also supported by the Wellcome ISSF COVID-19 Research Momentum fund (119293) and the University of Dundee. G.A.S. was supported by Wings for Life. C.P.P. was supported by the MRC (MC_UU_00007/15). A.P.M. was supported by the Chan Zuckerberg Biohub. E.L.-B. and J.F. were supported by the Swedish Research Council, Knut and Alice Wallenbergs Stiftelse, and the Swedish Cancer Foundation. The confocal microscope used for imaging was purchased with support from Wellcome Trust Multi-User Equipment grant (WT101468). Copyright: © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.

PY - 2023/2/6

Y1 - 2023/2/6

N2 - The adult spinal cord stem cell potential resides within the ependymal cell population and declines with age. Ependymal cells are, however, heterogeneous, and the biological diversity this represents and how it changes with age remain unknown. Here, we present a single-cell transcriptomic census of spinal cord ependymal cells from adult and aged mice, identifying not only all known ependymal cell subtypes but also immature as well as mature cell states. By comparing transcriptomes of spinal cord and brain ependymal cells, which lack stem cell abilities, we identify immature cells as potential spinal cord stem cells. Following spinal cord injury, these cells re-enter the cell cycle, which is accompanied by a short-lived reversal of ependymal cell maturation. We further analyze ependymal cells in the human spinal cord and identify widespread cell maturation and altered cell identities. This in-depth characterization of spinal cord ependymal cells provides insight into their biology and informs strategies for spinal cord repair.

AB - The adult spinal cord stem cell potential resides within the ependymal cell population and declines with age. Ependymal cells are, however, heterogeneous, and the biological diversity this represents and how it changes with age remain unknown. Here, we present a single-cell transcriptomic census of spinal cord ependymal cells from adult and aged mice, identifying not only all known ependymal cell subtypes but also immature as well as mature cell states. By comparing transcriptomes of spinal cord and brain ependymal cells, which lack stem cell abilities, we identify immature cells as potential spinal cord stem cells. Following spinal cord injury, these cells re-enter the cell cycle, which is accompanied by a short-lived reversal of ependymal cell maturation. We further analyze ependymal cells in the human spinal cord and identify widespread cell maturation and altered cell identities. This in-depth characterization of spinal cord ependymal cells provides insight into their biology and informs strategies for spinal cord repair.

KW - ependymal cell

KW - spinal cord

KW - spinal cord injury

KW - cell maturation

KW - adult neural stem cell

KW - mouse

KW - human

KW - scRNA-seq

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U2 - 10.1016/j.devcel.2023.01.003

DO - 10.1016/j.devcel.2023.01.003

M3 - Article

C2 - 36706756

SN - 1534-5807

VL - 58

SP - 239-255.e10

JO - Developmental Cell

JF - Developmental Cell

IS - 3

ER -

An ependymal cell census identifies heterogeneous and ongoing cell maturation in the adult mouse spinal cord that changes dynamically on injury

Abstract

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Unravelling the Molecular Heterogeneity within the Spinal Cord Stem Cell Niche by Single Cell Transcriptomics

Dissecting Spinal Cord Ependymal Cell Heterongeneity by Single-Cell Transciptomics (ECtomics) (Joint with MRC Institute of Genetics and Molecular Medicine and Sanger-EBI Single Cell Genomics Centre)

Code for the analysis of scRNA-seq data from spinal cord ependymal cells of young and aged mice

Single-cell RNA-sequencing of spinal cord ependymal cells from FOXJ1-EGFP mice

Single-cell transcriptomics of mouse spinal cord ependymal cells

RNA expression in the spinal cord at CS13 and CS18

Cite this

An ependymal cell census identifies heterogeneous and ongoing cell maturation in the adult mouse spinal cord that changes dynamically on injury

Abstract

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Projects

Unravelling the Molecular Heterogeneity within the Spinal Cord Stem Cell Niche by Single Cell Transcriptomics

Dissecting Spinal Cord Ependymal Cell Heterongeneity by Single-Cell Transciptomics (ECtomics) (Joint with MRC Institute of Genetics and Molecular Medicine and Sanger-EBI Single Cell Genomics Centre)

Research output

Code for the analysis of scRNA-seq data from spinal cord ependymal cells of young and aged mice

Datasets

Single-cell RNA-sequencing of spinal cord ependymal cells from FOXJ1-EGFP mice

Single-cell transcriptomics of mouse spinal cord ependymal cells

RNA expression in the spinal cord at CS13 and CS18

Cite this