Increased Tau Expression Correlates with Neuronal Maturation in the Developing Human Cerebral Cortex.

Autor:	Fiock KL; Department of Pathology, University of Iowa, Iowa City, IA 52242., Smalley ME; Department of Pathology, University of Iowa, Iowa City, IA 52242., Crary JF; Department of Pathology, Icahn School of Medicine at Mount Sinai, New York, NY 10029.; Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY.; Friedmann Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029., Pasca AM; Department of Pediatrics, Stanford University, Palo Alto, CA 94305., Hefti MM; Department of Pathology, University of Iowa, Iowa City, IA 52242 marco-hefti@uiowa.edu.; Iowa Neuroscience Institute, University of Iowa, Iowa City, IA 52242.; Interdisciplinary Neuroscience Graduate Program, University of Iowa, Iowa City, IA 52242.
Jazyk:	angličtina
Zdroj:	ENeuro [eNeuro] 2020 May 28; Vol. 7 (3). Date of Electronic Publication: 2020 May 28 (Print Publication: 2020).
DOI:	10.1523/ENEURO.0058-20.2020
Abstrakt:	Although best known for its role in Alzheimer's disease (AD), tau is expressed throughout brain development, although it remains unclear when and which cell types this expression occurs and how it affects disease states in both fetal and neonatal periods. We thus sought to map tau mRNA and protein expression in the developing human brain at the cellular level using a combination of existing single-cell RNA sequencing (sc-RNAseq) data, RNA in situ hybridization (RNAscope), and immunohistochemistry (IHC). Using sc-RNAseq, we found that tau mRNA expression begins in radial glia but increases dramatically as migrating neuronal precursors mature. Specifically, TBR1 + maturing neurons and SYN + mature neurons showed significantly higher mRNA expression than GFAP + / NES + radial glia or TBR2 + intermediate progenitors. By RNAscope, we found low levels of tau mRNA in subventricular zone (SVZ) radial glia and deep white matter intermediate progenitors, with an increase in more superficially located maturing and mature neurons. By total-tau IHC, the germinal matrix and SVZ showed little protein expression, although both RNAscope and sc-RNAseq showed mRNA, and Western blotting revealed significantly less protein in those areas compared with more mature regions. Induced pluripotent stem cell (iPSC)-derived cortical organoids showed a similar tau expression pattern by sc-RNAseq and RNAscope. Our results indicate that tau increases with neuronal maturation in both the developing fetal brain and iPSC-derived organoids and forms a basis for future research on regulatory mechanisms triggering the onset of tau gene transcription and translation, which may represent potential therapeutic targets for neurodegenerative tauopathies and neurodevelopmental disorders. (Copyright © 2020 Fiock et al.)
Databáze:	MEDLINE
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