Glial progenitor heterogeneity and key regulators revealed by single-cell RNA sequencing provide insight to regeneration in spinal cord injury

Summary: Recent studies have revealed the heterogeneous nature of astrocytes; however, how diverse constituents of astrocyte-lineage cells are regulated in adult spinal cord after injury and contribute to regeneration remains elusive. We perform single-cell RNA sequencing of GFAP-expressing cells fr...

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Main Authors: Haichao Wei, Xizi Wu, Joseph Withrow, Raquel Cuevas-Diaz Duran, Simranjit Singh, Lesley S. Chaboub, Jyotirmoy Rakshit, Julio Mejia, Andrew Rolfe, Juan J. Herrera, Philip J. Horner, Jia Qian Wu
Format: Article
Language:English
Published: Elsevier 2023-05-01
Series:Cell Reports
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2211124723004977
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author Haichao Wei
Xizi Wu
Joseph Withrow
Raquel Cuevas-Diaz Duran
Simranjit Singh
Lesley S. Chaboub
Jyotirmoy Rakshit
Julio Mejia
Andrew Rolfe
Juan J. Herrera
Philip J. Horner
Jia Qian Wu
author_facet Haichao Wei
Xizi Wu
Joseph Withrow
Raquel Cuevas-Diaz Duran
Simranjit Singh
Lesley S. Chaboub
Jyotirmoy Rakshit
Julio Mejia
Andrew Rolfe
Juan J. Herrera
Philip J. Horner
Jia Qian Wu
author_sort Haichao Wei
collection DOAJ
description Summary: Recent studies have revealed the heterogeneous nature of astrocytes; however, how diverse constituents of astrocyte-lineage cells are regulated in adult spinal cord after injury and contribute to regeneration remains elusive. We perform single-cell RNA sequencing of GFAP-expressing cells from sub-chronic spinal cord injury models and identify and compare with the subpopulations in acute-stage data. We find subpopulations with distinct functional enrichment and their identities defined by subpopulation-specific transcription factors and regulons. Immunohistochemistry, RNAscope experiments, and quantification by stereology verify the molecular signature, location, and morphology of potential resident neural progenitors or neural stem cells in the adult spinal cord before and after injury and uncover the populations of the intermediate cells enriched in neuronal genes that could potentially transition into other subpopulations. This study has expanded the knowledge of the heterogeneity and cell state transition of glial progenitors in adult spinal cord before and after injury.
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spelling doaj.art-37e008278b61471b9bacf142fa28baf82023-05-08T04:09:18ZengElsevierCell Reports2211-12472023-05-01425112486Glial progenitor heterogeneity and key regulators revealed by single-cell RNA sequencing provide insight to regeneration in spinal cord injuryHaichao Wei0Xizi Wu1Joseph Withrow2Raquel Cuevas-Diaz Duran3Simranjit Singh4Lesley S. Chaboub5Jyotirmoy Rakshit6Julio Mejia7Andrew Rolfe8Juan J. Herrera9Philip J. Horner10Jia Qian Wu11The Department of Neurosurgery, McGovern Medical School, The University of Texas Health Science Center at Houston (UTHealth), Houston, TX 77030, USA; Center for Stem Cell and Regenerative Medicine, UT Brown Foundation Institute of Molecular Medicine, Houston, TX 77030, USAThe Department of Neurosurgery, McGovern Medical School, The University of Texas Health Science Center at Houston (UTHealth), Houston, TX 77030, USA; Center for Stem Cell and Regenerative Medicine, UT Brown Foundation Institute of Molecular Medicine, Houston, TX 77030, USAThe Department of Neurosurgery, McGovern Medical School, The University of Texas Health Science Center at Houston (UTHealth), Houston, TX 77030, USATecnologico de Monterrey, Escuela de Medicina y Ciencias de la Salud, Monterrey, Nuevo León 64710, MexicoThe Department of Neurosurgery, McGovern Medical School, The University of Texas Health Science Center at Houston (UTHealth), Houston, TX 77030, USA; Center for Stem Cell and Regenerative Medicine, UT Brown Foundation Institute of Molecular Medicine, Houston, TX 77030, USACenter for Neuroregeneration, Department of Neurosurgery, Houston Methodist Research Institute, Houston, TX 77030, USAThe Department of Neurosurgery, McGovern Medical School, The University of Texas Health Science Center at Houston (UTHealth), Houston, TX 77030, USA; Center for Stem Cell and Regenerative Medicine, UT Brown Foundation Institute of Molecular Medicine, Houston, TX 77030, USACenter for Neuroregeneration, Department of Neurosurgery, Houston Methodist Research Institute, Houston, TX 77030, USAThe Department of Neurosurgery, McGovern Medical School, The University of Texas Health Science Center at Houston (UTHealth), Houston, TX 77030, USA; Center for Stem Cell and Regenerative Medicine, UT Brown Foundation Institute of Molecular Medicine, Houston, TX 77030, USADepartment of Diagnostic and Interventional Imaging, McGovern Medical School, UTHealth, Houston, TX 77030, USACenter for Neuroregeneration, Department of Neurosurgery, Houston Methodist Research Institute, Houston, TX 77030, USA; Corresponding authorThe Department of Neurosurgery, McGovern Medical School, The University of Texas Health Science Center at Houston (UTHealth), Houston, TX 77030, USA; Center for Stem Cell and Regenerative Medicine, UT Brown Foundation Institute of Molecular Medicine, Houston, TX 77030, USA; MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences, Houston, TX 77030, USA; Corresponding authorSummary: Recent studies have revealed the heterogeneous nature of astrocytes; however, how diverse constituents of astrocyte-lineage cells are regulated in adult spinal cord after injury and contribute to regeneration remains elusive. We perform single-cell RNA sequencing of GFAP-expressing cells from sub-chronic spinal cord injury models and identify and compare with the subpopulations in acute-stage data. We find subpopulations with distinct functional enrichment and their identities defined by subpopulation-specific transcription factors and regulons. Immunohistochemistry, RNAscope experiments, and quantification by stereology verify the molecular signature, location, and morphology of potential resident neural progenitors or neural stem cells in the adult spinal cord before and after injury and uncover the populations of the intermediate cells enriched in neuronal genes that could potentially transition into other subpopulations. This study has expanded the knowledge of the heterogeneity and cell state transition of glial progenitors in adult spinal cord before and after injury.http://www.sciencedirect.com/science/article/pii/S2211124723004977CP: NeuroscienceCP: Stem cell research
spellingShingle Haichao Wei
Xizi Wu
Joseph Withrow
Raquel Cuevas-Diaz Duran
Simranjit Singh
Lesley S. Chaboub
Jyotirmoy Rakshit
Julio Mejia
Andrew Rolfe
Juan J. Herrera
Philip J. Horner
Jia Qian Wu
Glial progenitor heterogeneity and key regulators revealed by single-cell RNA sequencing provide insight to regeneration in spinal cord injury
Cell Reports
CP: Neuroscience
CP: Stem cell research
title Glial progenitor heterogeneity and key regulators revealed by single-cell RNA sequencing provide insight to regeneration in spinal cord injury
title_full Glial progenitor heterogeneity and key regulators revealed by single-cell RNA sequencing provide insight to regeneration in spinal cord injury
title_fullStr Glial progenitor heterogeneity and key regulators revealed by single-cell RNA sequencing provide insight to regeneration in spinal cord injury
title_full_unstemmed Glial progenitor heterogeneity and key regulators revealed by single-cell RNA sequencing provide insight to regeneration in spinal cord injury
title_short Glial progenitor heterogeneity and key regulators revealed by single-cell RNA sequencing provide insight to regeneration in spinal cord injury
title_sort glial progenitor heterogeneity and key regulators revealed by single cell rna sequencing provide insight to regeneration in spinal cord injury
topic CP: Neuroscience
CP: Stem cell research
url http://www.sciencedirect.com/science/article/pii/S2211124723004977
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