Journal article
Increased Tau Expression Correlates with Neuronal Maturation in the Developing Human Cerebral Cortex
eNeuro, Vol.7(3), p.ENEURO.0058-20.2020
05/01/2020
DOI: 10.1523/ENEURO.0058-20.2020
PMCID: PMC7262004
PMID: 32393582
Abstract
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.
Details
- Title: Subtitle
- Increased Tau Expression Correlates with Neuronal Maturation in the Developing Human Cerebral Cortex
- Creators
- Kimberly L Fiock - Department of PathologyMartin E Smalley - Department of PathologyJohn F Crary - Department of PathologyAnca M Pasca - Department of PediatricsMarco M Hefti - Department of Pathology
- Resource Type
- Journal article
- Publication Details
- eNeuro, Vol.7(3), p.ENEURO.0058-20.2020
- DOI
- 10.1523/ENEURO.0058-20.2020
- PMID
- 32393582
- PMCID
- PMC7262004
- NLM abbreviation
- eNeuro
- ISSN
- 2373-2822
- eISSN
- 2373-2822
- Publisher
- Society for Neuroscience
- Grant note
- Williams Cannon Foundation UL1TR002537; K23NS109284 / HHS | NIH | National Institute of Neurological Disorders and Stroke (NINDS)
- Language
- English
- Date published
- 05/01/2020
- Academic Unit
- Pathology; Iowa Neuroscience Institute; Radiation Oncology
- Record Identifier
- 9984070294102771
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