Developmental Origins of Human Cortical Oligodendrocytes and Astrocytes

Overview

Journal Neurosci Bull

Specialty Neurology

Date 2021 Aug 10

PMID 34374948

Citations 32

Authors

Lin Yang

Zhenmeiyu Li

Guoping Liu

Xiaosu Li

Zhengang Yang

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

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References

Anthony T, Klein C, Fishell G, Heintz N . Radial glia serve as neuronal progenitors in all regions of the central nervous system. Neuron. 2004; 41(6):881-90. DOI: 10.1016/s0896-6273(04)00140-0. View

Kriegstein A, Alvarez-Buylla A . The glial nature of embryonic and adult neural stem cells. Annu Rev Neurosci. 2009; 32:149-84. PMC: 3086722. DOI: 10.1146/annurev.neuro.051508.135600. View

Noctor S, Flint A, Weissman T, Dammerman R, Kriegstein A . Neurons derived from radial glial cells establish radial units in neocortex. Nature. 2001; 409(6821):714-20. DOI: 10.1038/35055553. View

Rakic P . Elusive radial glial cells: historical and evolutionary perspective. Glia. 2003; 43(1):19-32. DOI: 10.1002/glia.10244. View

Rakic P . A century of progress in corticoneurogenesis: from silver impregnation to genetic engineering. Cereb Cortex. 2006; 16 Suppl 1:i3-17. DOI: 10.1093/cercor/bhk036. View

Li X, Liu G, Yang L, Li Z, Zhang Z, Xu Z . Decoding Cortical Glial Cell Development. Neurosci Bull. 2021; 37(4):440-460. PMC: 8055813. DOI: 10.1007/s12264-021-00640-9. View

Gao P, Postiglione M, Krieger T, Hernandez L, Wang C, Han Z . Deterministic progenitor behavior and unitary production of neurons in the neocortex. Cell. 2014; 159(4):775-88. PMC: 4225456. DOI: 10.1016/j.cell.2014.10.027. View

Guo C, Eckler M, McKenna W, McKinsey G, Rubenstein J, Chen B . Fezf2 expression identifies a multipotent progenitor for neocortical projection neurons, astrocytes, and oligodendrocytes. Neuron. 2013; 80(5):1167-74. PMC: 3857588. DOI: 10.1016/j.neuron.2013.09.037. View

Shen Z, Lin Y, Yang J, Jorg D, Peng Y, Zhang X . Distinct progenitor behavior underlying neocortical gliogenesis related to tumorigenesis. Cell Rep. 2021; 34(11):108853. DOI: 10.1016/j.celrep.2021.108853. View

10.

Gal J, Morozov Y, Ayoub A, Chatterjee M, Rakic P, Haydar T . Molecular and morphological heterogeneity of neural precursors in the mouse neocortical proliferative zones. J Neurosci. 2006; 26(3):1045-56. PMC: 3249619. DOI: 10.1523/JNEUROSCI.4499-05.2006. View

11.

Tyler W, Haydar T . Multiplex genetic fate mapping reveals a novel route of neocortical neurogenesis, which is altered in the Ts65Dn mouse model of Down syndrome. J Neurosci. 2013; 33(12):5106-19. PMC: 3785112. DOI: 10.1523/JNEUROSCI.5380-12.2013. View

12.

Stancik E, Navarro-Quiroga I, Sellke R, Haydar T . Heterogeneity in ventricular zone neural precursors contributes to neuronal fate diversity in the postnatal neocortex. J Neurosci. 2010; 30(20):7028-36. PMC: 2909740. DOI: 10.1523/JNEUROSCI.6131-09.2010. View

13.

Kawaguchi A, Ikawa T, Kasukawa T, Ueda H, Kurimoto K, Saitou M . Single-cell gene profiling defines differential progenitor subclasses in mammalian neurogenesis. Development. 2008; 135(18):3113-24. DOI: 10.1242/dev.022616. View

14.

Reillo I, de Juan Romero C, Cardenas A, Clasca F, Martinez-Martinez M, Borrell V . A Complex Code of Extrinsic Influences on Cortical Progenitor Cells of Higher Mammals. Cereb Cortex. 2017; 27(9):4586-4606. DOI: 10.1093/cercor/bhx171. View

15.

Betizeau M, Cortay V, Patti D, Pfister S, Gautier E, Bellemin-Menard A . Precursor diversity and complexity of lineage relationships in the outer subventricular zone of the primate. Neuron. 2013; 80(2):442-57. DOI: 10.1016/j.neuron.2013.09.032. View

16.

Lv X, Ren S, Zhang X, Shen Z, Ghosh T, Xianyu A . TBR2 coordinates neurogenesis expansion and precise microcircuit organization via Protocadherin 19 in the mammalian cortex. Nat Commun. 2019; 10(1):3946. PMC: 6718393. DOI: 10.1038/s41467-019-11854-x. View

17.

Hevner R . Intermediate progenitors and Tbr2 in cortical development. J Anat. 2019; 235(3):616-625. PMC: 6656625. DOI: 10.1111/joa.12939. View

18.

Lin Y, Yang J, Shen Z, Ma J, Simons B, Shi S . Behavior and lineage progression of neural progenitors in the mammalian cortex. Curr Opin Neurobiol. 2020; 66:144-157. PMC: 8058148. DOI: 10.1016/j.conb.2020.10.017. View

19.

Huang H, Rubenstein J, Qiu M . Cracking the Codes of Cortical Glial Progenitors: Evidence for the Common Lineage of Astrocytes and Oligodendrocytes. Neurosci Bull. 2021; 37(6):437-439. PMC: 8055804. DOI: 10.1007/s12264-021-00675-y. View

20.

Lui J, Hansen D, Kriegstein A . Development and evolution of the human neocortex. Cell. 2011; 146(1):18-36. PMC: 3610574. DOI: 10.1016/j.cell.2011.06.030. View