Cracking the Codes of Cortical Glial Progenitors: Evidence for the Common Lineage of Astrocytes and Oligodendrocytes

Huang, Hao; Rubenstein, John L.R.; Qiu, Mengsheng

doi:10.1007/s12264-021-00675-y

Cited by 9 publications

(6 citation statements)

References 14 publications

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“…6 A). Among the Nestin + cells derived from the dedifferentiation of astrocytes, some might even dedifferentiate to the stage of basal multipotent intermediate progenitor cells (Huang et al 2021 ). While this study demonstrated that EGF can induce the expression of oligodendrogenic genes Olig1 and Olig2, we previously demonstrated that Sox10 activity can stimulate Olig2 expression in neural progenitor cells to enhance oligodendrogenesis (Liu et al 2007 ).…”

Section: Discussionmentioning

confidence: 99%

EGF signaling promotes the lineage conversion of astrocytes into oligodendrocytes

Liu

et al. 2022

Mol Med

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Background The conversion of astrocytes activated by nerve injuries to oligodendrocytes is not only beneficial to axonal remyelination, but also helpful for reversal of glial scar. Recent studies have shown that pathological niche promoted the Sox10-mediated astrocytic transdifferentiation to oligodendrocytes. The extracellular factors underlying the cell fate switching are not known. Methods Astrocytes were obtained from mouse spinal cord dissociation culture and purified by differential adherent properties. The lineage conversion of astrocytes into oligodendrocyte lineage cells was carried out by Sox10-expressing virus infection both in vitro and in vivo, meanwhile, epidermal growth factor (EGF) and epidermal growth factor receptor (EGFR) inhibitor Gefitinib were adopted to investigate the function of EGF signaling in this fate transition process. Pharmacological inhibition analyses were performed to examine the pathway connecting the EGF with the expression of oligodendrogenic genes and cell fate transdifferentiation. Results EGF treatment facilitated the Sox10-induced transformation of astrocytes to O4+ induced oligodendrocyte precursor cells (iOPCs) in vitro. The transdifferentiation of astrocytes to iOPCs went through two distinct but interconnected processes: (1) dedifferentiation of astrocytes to astrocyte precursor cells (APCs); (2) transformation of APCs to iOPCs, EGF signaling was involved in both processes. And EGF triggered astrocytes to express oligodendrogenic genes Olig1 and Olig2 by activating extracellular signal-regulated kinase 1 and 2 (Erk1/2) pathway. In addition, we discovered that EGF can enhance astrocyte transdifferentiation in injured spinal cord tissues. Conclusions These findings provide strong evidence that EGF facilitates the transdifferentiation of astrocytes to oligodendrocytes, and suggest that targeting the EGF-EGFR-Erk1/2 signaling axis may represent a novel therapeutic strategy for myelin repair in injured central nervous system (CNS) tissues.

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Section: Discussionmentioning

confidence: 99%

EGF signaling promotes the lineage conversion of astrocytes into oligodendrocytes

Liu

et al. 2022

Mol Med

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“…In the brain, OLIG2 is broadly expressed in the VZ of the ventral telencephalon, including the LGE, MGE, and AEP regions at embryonic stages [37][38][39]. In the dorsal cortical region, the earliest OLIG2positive cells appear at ~ E17.5, coincident with the onset of local gliogenesis [40,41]. These OLIG2+ pluripotent precursor cells, termed multipotent intermediate progenitor cells (MIPCs) (also named pri-OPCs or pre-OPCs in other studies [42,43]), are the common precursors of cortexderived astrocytes, oligodendrocytes, and olfactory bulb interneurons (OBiNs) [40,44] (OLIG2+ cells in the VZ and subventricular zone (SVZ), Fig.…”

Section: Olig2mentioning

confidence: 99%

Immunological Markers for Central Nervous System Glia

Huang

Tang

et al. 2022

Neurosci. Bull.

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Glial cells in the central nervous system (CNS) are composed of oligodendrocytes, astrocytes and microglia. They contribute more than half of the total cells of the CNS, and are essential for neural development and functioning. Studies on the fate specification, differentiation, and functional diversification of glial cells mainly rely on the proper use of cell- or stage-specific molecular markers. However, as cellular markers often exhibit different specificity and sensitivity, careful consideration must be given prior to their application to avoid possible confusion. Here, we provide an updated overview of a list of well-established immunological markers for the labeling of central glia, and discuss the cell-type specificity and stage dependency of their expression.

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“…bMIPCs undergo several rounds of mitosis and generate cortical oligodendrocyte-lineage-restricted IPCs (OPCs), astrocyte lineage-restricted IPCs (APCs), and OBiN lineage-restricted IPCs (OBiN-IPCs). These lineage-restricted IPCs then divide symmetrically to generate cortical astrocytes, oligodendrocytes and OBiNs, respectively [ 6 , 20 ].…”

Section: Introductionmentioning

confidence: 99%

Developmental Origins of Human Cortical Oligodendrocytes and Astrocytes

Yang

Liu

et al. 2021

Neurosci. Bull.

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Human cortical radial glial cells are primary neural stem cells that give rise to cortical glutaminergic projection pyramidal neurons, glial cells (oligodendrocytes and astrocytes) and olfactory bulb GABAergic interneurons. One of prominent features of the human cortex is enriched with glial cells, but there are major gaps in understanding how these glial cells are generated. Herein, by integrating analysis of published human cortical single-cell RNA-Seq datasets with our immunohistochemistical analyses, we show that around gestational week 18, EGFR-expressing human cortical truncated radial glial cells (tRGs) give rise to basal multipotent intermediate progenitors (bMIPCs) that express EGFR, ASCL1, OLIG2 and OLIG1. These bMIPCs undergo several rounds of mitosis and generate cortical oligodendrocytes, astrocytes and olfactory bulb interneurons. We also characterized molecular features of the cortical tRG. Integration of our findings suggests a general picture of the lineage progression of cortical radial glial cells, a fundamental process of the developing human cerebral cortex.

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Cracking the Codes of Cortical Glial Progenitors: Evidence for the Common Lineage of Astrocytes and Oligodendrocytes

Cited by 9 publications

References 14 publications

EGF signaling promotes the lineage conversion of astrocytes into oligodendrocytes

EGF signaling promotes the lineage conversion of astrocytes into oligodendrocytes

Immunological Markers for Central Nervous System Glia

Developmental Origins of Human Cortical Oligodendrocytes and Astrocytes

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