What Have Advances in Transcriptomic Technologies Taught us About Human White Matter Pathologies?

Sarah Jäkel,Anna Williams

doi:10.3389/fncel.2020.00238

Abstract

For a long time, post-mortem analysis of human brain pathologies has been purely descriptive, limiting insight into the pathological mechanisms. However, starting in the early 2000s, next-generation sequencing (NGS) and the routine application of bulk RNA-sequencing and microarray technologies have revolutionized the usefulness of post-mortem human brain tissue. This has allowed many studies to provide novel mechanistic insights into certain brain pathologies, albeit at a still unsatisfying resolution, with masking of lowly expressed genes and regulatory elements in different cell types. The recent rapid evolution of single-cell technologies has now allowed researchers to shed light on human pathologies at a previously unreached resolution revealing further insights into pathological mechanisms that will open the way for the development of new strategies for therapies. In this review article, we will give an overview of the incremental information that single-cell technologies have given us for human white matter (WM) pathologies, summarize which single-cell technologies are available, and speculate where these novel approaches may lead us for pathological assessment in the future.

Highlights

Classical Approaches to Study Human White Matter PathologyModern neuropathology has its origins in the late 19th and early 20th century when famous neurologists or psychologists such as Santiago Ramon y Cajal, Jean-Martin Charcot, and Alois Alzheimer started to describe and illustrate the central nervous system (CNS) and its pathological changes
Multiple Sclerosis (MS), a chronic inflammatory and demyelinating neurodegenerative disease of the CNS, is a good example of how this descriptive pathology is still used, but it applies to other pathologies
Specific magnetic resonance imaging sequences enable the detection of chronic active lesions where acute inflammation is happening at the lesion rim (Absinta et al, 2018) and these are associated with disability and ongoing tissue damage (Absinta et al, 2019) aiding prognosis

Summary

Introduction

Classical Approaches to Study Human White Matter PathologyModern neuropathology has its origins in the late 19th and early 20th century when famous neurologists or psychologists such as Santiago Ramon y Cajal, Jean-Martin Charcot, and Alois Alzheimer started to describe and illustrate the central nervous system (CNS) and its pathological changes. With the development of new technologies in the 2000s, many labs started to use bulk RNA-sequencing (RNA-seq) or DNA-based microarrays to describe cellular and molecular changes in disease at the transcript level, to gain a deeper insight into functional pathological changes.

Results

Conclusion