Systematic Analysis of Purified Astrocytes After SCI Unveils Zeb2os Function During Astrogliosis

Overview

Journal Cell Rep

Publisher Cell Press

Specialties Biology
Cell Biology
Molecular Biology

Date 2021 Feb 3

PMID 33535036

Citations 13

Authors

Haichao Wei

Xizi Wu

Yanan You

Raquel Cuevas-Diaz Duran

Yiyan Zheng

K Lakshmi Narayanan

Bo Hai

Xu Li

Neha Tallapragada

Tanuj J Prajapati

Dong H Kim

Benjamin Deneen

Qi-Lin Cao

Jia Qian Wu

Affiliations

Soon will be listed here.

Abstract

Spinal cord injury (SCI) is one of the most devastating neural injuries without effective therapeutic solutions. Astrocytes are the predominant component of the scar. Understanding the complex contributions of reactive astrocytes to SCI pathophysiologies is fundamentally important for developing therapeutic strategies. We have studied the molecular changes in the injury environment and the astrocyte-specific responses by astrocyte purification from injured spinal cords from acute to chronic stages. In addition to protein-coding genes, we have systematically analyzed the expression profiles of long non-coding RNAs (lncRNAs) (>200 bp), which are regulatory RNAs that play important roles in the CNS. We have identified a highly conserved lncRNA, Zeb2os, and demonstrated using functional assays that it plays an important role in reactive astrogliosis through the Zeb2os/Zeb2/Stat3 axis. These studies provide valuable insights into the molecular basis of reactive astrogliosis and fill the knowledge gap regarding the function(s) of lncRNAs in astrogliosis and SCI.

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References

Novikova I, Hennelly S, Sanbonmatsu K . Structural architecture of the human long non-coding RNA, steroid receptor RNA activator. Nucleic Acids Res. 2012; 40(11):5034-51. PMC: 3367176. DOI: 10.1093/nar/gks071. View

Barres B . The mystery and magic of glia: a perspective on their roles in health and disease. Neuron. 2008; 60(3):430-40. DOI: 10.1016/j.neuron.2008.10.013. View

Liddelow S, Barres B . Reactive Astrocytes: Production, Function, and Therapeutic Potential. Immunity. 2017; 46(6):957-967. DOI: 10.1016/j.immuni.2017.06.006. View

Weng Q, Chen Y, Wang H, Xu X, Yang B, He Q . Dual-mode modulation of Smad signaling by Smad-interacting protein Sip1 is required for myelination in the central nervous system. Neuron. 2012; 73(4):713-28. PMC: 3293152. DOI: 10.1016/j.neuron.2011.12.021. View

Ljungberg M, Ali Y, Zhu J, Wu C, Oka K, Zhai R . CREB-activity and nmnat2 transcription are down-regulated prior to neurodegeneration, while NMNAT2 over-expression is neuroprotective, in a mouse model of human tauopathy. Hum Mol Genet. 2011; 21(2):251-67. PMC: 3276285. DOI: 10.1093/hmg/ddr492. View

Anders S, Pyl P, Huber W . HTSeq--a Python framework to work with high-throughput sequencing data. Bioinformatics. 2014; 31(2):166-9. PMC: 4287950. DOI: 10.1093/bioinformatics/btu638. View

Ben Haim L, Ceyzeriat K, Carrillo-de Sauvage M, Aubry F, Auregan G, Guillermier M . The JAK/STAT3 pathway is a common inducer of astrocyte reactivity in Alzheimer's and Huntington's diseases. J Neurosci. 2015; 35(6):2817-29. PMC: 6605603. DOI: 10.1523/JNEUROSCI.3516-14.2015. View

Wu L, Wang J, Conidi A, Zhao C, Wang H, Ford Z . Zeb2 recruits HDAC-NuRD to inhibit Notch and controls Schwann cell differentiation and remyelination. Nat Neurosci. 2016; 19(8):1060-72. PMC: 4961522. DOI: 10.1038/nn.4322. View

Butenschon J, Zimmermann T, Schmarowski N, Nitsch R, Fackelmeier B, Friedemann K . PSA-NCAM positive neural progenitors stably expressing BDNF promote functional recovery in a mouse model of spinal cord injury. Stem Cell Res Ther. 2016; 7:11. PMC: 4712602. DOI: 10.1186/s13287-015-0268-x. View

10.

Bundesen L, Scheel T, Bregman B, Kromer L . Ephrin-B2 and EphB2 regulation of astrocyte-meningeal fibroblast interactions in response to spinal cord lesions in adult rats. J Neurosci. 2003; 23(21):7789-800. PMC: 6740614. View

11.

Cabili M, Trapnell C, Goff L, Koziol M, Tazon-Vega B, Regev A . Integrative annotation of human large intergenic noncoding RNAs reveals global properties and specific subclasses. Genes Dev. 2011; 25(18):1915-27. PMC: 3185964. DOI: 10.1101/gad.17446611. View

12.

Khakh B, Sofroniew M . Diversity of astrocyte functions and phenotypes in neural circuits. Nat Neurosci. 2015; 18(7):942-52. PMC: 5258184. DOI: 10.1038/nn.4043. View

13.

Wanner I, Anderson M, Song B, Levine J, Fernandez A, Gray-Thompson Z . Glial scar borders are formed by newly proliferated, elongated astrocytes that interact to corral inflammatory and fibrotic cells via STAT3-dependent mechanisms after spinal cord injury. J Neurosci. 2013; 33(31):12870-86. PMC: 3728693. DOI: 10.1523/JNEUROSCI.2121-13.2013. View

14.

Filous A, Silver J . "Targeting astrocytes in CNS injury and disease: A translational research approach". Prog Neurobiol. 2016; 144:173-87. PMC: 5035184. DOI: 10.1016/j.pneurobio.2016.03.009. View

15.

Schmeier S, Alam T, Essack M, Bajic V . TcoF-DB v2: update of the database of human and mouse transcription co-factors and transcription factor interactions. Nucleic Acids Res. 2016; 45(D1):D145-D150. PMC: 5210517. DOI: 10.1093/nar/gkw1007. View

16.

Cheng X, Zheng Y, Bu P, Qi X, Fan C, Li F . Apolipoprotein E as a novel therapeutic neuroprotection target after traumatic spinal cord injury. Exp Neurol. 2017; 299(Pt A):97-108. PMC: 5967384. DOI: 10.1016/j.expneurol.2017.10.014. View

17.

Zhang Y, Chen K, Sloan S, Bennett M, Scholze A, OKeeffe S . An RNA-sequencing transcriptome and splicing database of glia, neurons, and vascular cells of the cerebral cortex. J Neurosci. 2014; 34(36):11929-47. PMC: 4152602. DOI: 10.1523/JNEUROSCI.1860-14.2014. View

18.

Su Z, Niu W, Liu M, Zou Y, Zhang C . In vivo conversion of astrocytes to neurons in the injured adult spinal cord. Nat Commun. 2014; 5:3338. PMC: 3966078. DOI: 10.1038/ncomms4338. View

19.

Chen K, Deng S, Lu H, Zheng Y, Yang G, Kim D . RNA-seq characterization of spinal cord injury transcriptome in acute/subacute phases: a resource for understanding the pathology at the systems level. PLoS One. 2013; 8(8):e72567. PMC: 3739761. DOI: 10.1371/journal.pone.0072567. View

20.

Li Z, Ho I, Li X, Xu D, Wu W, Chan M . Long non-coding RNAs in the spinal cord injury: Novel spotlight. J Cell Mol Med. 2019; 23(8):4883-4890. PMC: 6653026. DOI: 10.1111/jcmm.14422. View