Versatile subtypes of pericytes and their roles in spinal cord injury repair, bone development and repair

Zhu, Sipin; Chen, Min; Ying, Yibo; Wu, Qiuji; Huang, Zhiyang; Ni, Wenfei; Wang, Xiangyang; Xu, Huazi; Bennett, Samuel; Xiao, Jian; Xu, Jiake

doi:10.1038/s41413-022-00203-2

Cited by 43 publications

(30 citation statements)

References 151 publications

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“…Recent studies have uncovered a subtype of perivascular cells whose markers include platelet-derived growth factor receptor beta (Pdgfrβ) and NG2. These perivascular cells exhibit mesenchymal stem-cell properties and are involved in spinal cord injury repair (Zhu et al 2022). Nevertheless, NG2 glia are also characterized by Pdgfrα expression (reviewed in (Nishiyama et al 2016)), and therefore we used immunodetection of Pdgfrα to distinguish these cells from NG2 + perivascular cells.…”

Section: Resultsmentioning

confidence: 99%

Astrocyte-like subpopulation of NG2 glia in the adult mouse cortex exhibits characteristics of neural progenitor cells and is capable of forming neuron-like cells after ischemic injury

Janečková

Knotek

Kriška

et al. 2023

Preprint

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Glia cells expressing neuron-glial antigen 2 (NG2) play a critical role as oligodendrocyte precursor cells (OPCs) in the healthy brain; however, their differentiation potential after ischemic injury remains an unresolved question. Here, we aimed to elucidate the heterogeneity and role of NG2 glia in the ischemic brain. We used transgenic mice to label NG2-expressing cells and their progeny with red fluorescent protein tdTomato in the healthy brains and those after focal cerebral ischemia (FCI). Based on single-cell RNA sequencing, the labeled glial cells were divided into five distinct subpopulations. The identity of these subpopulations was determined based on gene expression patterns. In addition, membrane properties were further analyzed using the patch-clamp technique. Three of the observed subpopulations represented OPCs, whereas the fourth group exhibited characteristics of cells destined for oligodendrocyte fate. The fifth subpopulation of NG2 glia carried astrocytic markers. Importantly, we detected features of neural progenitors in these cells. This subpopulation was present in both healthy and post-ischemic tissue; however, its gene expression changed after ischemia, with genes related to neurogenesis being more abundant. Neurogenic gene expression was monitored over time and complemented by immunohistochemical staining, which showed increased numbers of Purkinje cell protein 4-positive NG2 cells at the edge of the ischemic lesion 12 days after FCI, and NeuN-positive NG2 cells 28 days after injury, indicating the existence of neuron-like cells that develop from NG2 glia in the ischemic tissue. Our results provide further insight into the differentiation plasticity and neurogenic potential of NG2 glia after stroke.

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Section: Resultsmentioning

confidence: 99%

Astrocyte-like subpopulation of NG2 glia in the adult mouse cortex exhibits characteristics of neural progenitor cells and is capable of forming neuron-like cells after ischemic injury

Janečková

Knotek

Kriška

et al. 2023

Preprint

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show abstract

“…Type A pericytes are abluminal to Type B pericytes, with Type B expressing desmin and αSMA in addition to other pericyte markers [ 44 ]. Despite these observations and many other studies regarding different subtypes of pericytes [ 89 ], a recent scRNA-seq study did not identify pericytes subtypes in mouse brain vasculature [ 65 ]. However, two distinct subtypes have been identified in the human brain by scRNA-seq [ 74 ].…”

Section: The Cellular Origins Of Fibroblasts In the Fibrotic Scarmentioning

confidence: 91%

Fibrotic Scar in CNS Injuries: From the Cellular Origins of Fibroblasts to the Molecular Processes of Fibrotic Scar Formation

Ayazi

Zivkovic

Hammel

et al. 2022

Cells

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Central nervous system (CNS) trauma activates a persistent repair response that leads to fibrotic scar formation within the lesion. This scarring is similar to other organ fibrosis in many ways; however, the unique features of the CNS differentiate it from other organs. In this review, we discuss fibrotic scar formation in CNS trauma, including the cellular origins of fibroblasts, the mechanism of fibrotic scar formation following an injury, as well as the implication of the fibrotic scar in CNS tissue remodeling and regeneration. While discussing the shared features of CNS fibrotic scar and fibrosis outside the CNS, we highlight their differences and discuss therapeutic targets that may enhance regeneration in the CNS.

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“…Pericytes are involved in the establishment of the blood-brain barrier and the blood-spinal cord barrier, as well as the stability of the internal environment of the brain and spinal cord (Cheng et al, 2018;Sweeney et al, 2019). Previous studies have shown that pericytes are closely related to the formation of scars and the recovery of function after SCI (Dias et al, 2018;Hesp et al, 2018;Zhu et al, 2022). Some studies have confirmed that m6A modification in pericytes is involved in the occurrence and development of hypertension and diabetes (Wu Q. et al, 2019;Suo et al, 2022).…”

Section: N6-methyladenosine Modification and Scarring After Spinal Co...mentioning

confidence: 99%

N6-methyladenosine modification: A potential regulatory mechanism in spinal cord injury

Liu

Fan²,

Li³

et al. 2022

Front. Cell. Neurosci.

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N6-methyladenosine (m6A), an essential post-transcriptional modification in eukaryotes, is closely related to the development of pathological processes in neurological diseases. Notably, spinal cord injury (SCI) is a serious traumatic disease of the central nervous system, with a complex pathological mechanism which is still not completely understood. Recent studies have found that m6A modification levels are changed after SCI, and m6A-related regulators are involved in the changes of the local spinal cord microenvironment after injury. However, research on the role of m6A modification in SCI is still in the early stages. This review discusses the latest progress in the dynamic regulation of m6A modification, including methyltransferases (“writers”), demethylases (“erasers”) and m6A -binding proteins (“readers”). And then analyses the pathological mechanism relationship between m6A and the microenvironment after SCI. The biological processes involved included cell death, axon regeneration, and scar formation, which provides new insight for future research on the role of m6A modification in SCI and the clinical transformation of strategies for promoting recovery of spinal cord function.

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Versatile subtypes of pericytes and their roles in spinal cord injury repair, bone development and repair

Cited by 43 publications

References 151 publications

Astrocyte-like subpopulation of NG2 glia in the adult mouse cortex exhibits characteristics of neural progenitor cells and is capable of forming neuron-like cells after ischemic injury

Astrocyte-like subpopulation of NG2 glia in the adult mouse cortex exhibits characteristics of neural progenitor cells and is capable of forming neuron-like cells after ischemic injury

Fibrotic Scar in CNS Injuries: From the Cellular Origins of Fibroblasts to the Molecular Processes of Fibrotic Scar Formation

N6-methyladenosine modification: A potential regulatory mechanism in spinal cord injury

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