summary: New research examines the regenerative capacity of the human brain in aging and neurological disease and may offer an alternative to traditional strategies to enhance or restore brain function. Recent single-cell transcriptome studies in the adult hippocampus have yielded conflicting results, and investigators believe that the design, analysis, and interpretation of these studies in the adult hippocampus address specific issues that require particular attention. I’ve found that it can be confusing by Open discussion on site.
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Can our brain regenerate? And can this regenerative capacity be harnessed in aging and neurodegenerative conditions? These questions have sparked intense debate in neuroscience over the years.
A new study from the Dutch Institute for Neuroscience shows why conflicting results exist and proposes a roadmap on how to solve these problems.
The concept of harnessing the regenerative potential of the human brain in aging and neurological disease may enhance brain function, especially given the current lack of effective therapeutic strategies in neurodegenerative diseases such as Alzheimer’s disease. or a particularly attractive alternative to traditional strategies for recovery.
The question of whether the human brain has the ability to regenerate has been at the center of intense scientific debate for many years, and recent research has yielded conflicting results.
A new study by Giorgia Tosoni and Dilara Ayyildiz, under the supervision of Evgenia Salta in the Laboratory of Neurodevelopment and Neurodegeneration, critically discusses and reanalyzes previously published datasets. How is it that no clear answer to this mystery has yet been found?
A previous study in which dividing cells were labeled in the post-mortem human brain showed that new cells can indeed arise in the hippocampus of our brain throughout adulthood.
However, other studies contradict these results and fail to detect new brain cell generation in this region. may have contributed to the results. Therefore, elucidating the extent of human brain regeneration remains a challenge.
new state-of-the-art technology
Recent advances in single-cell transcriptomics techniques have provided valuable insight into the different cell types found in human brains from deceased donors with various brain diseases.
To date, single-cell transcriptome techniques have been used to characterize rare cell populations in the human brain. In addition to identifying specific cell types, mononuclear RNA-sequencing can also investigate specific gene expression profiles to fully unravel the cellular complexity of the hippocampus.
The emergence of single-cell transcriptomics technology was initially seen as a panacea for resolving the controversies in this field. However, recent single-cell RNA-sequencing studies in the human hippocampus yielded conflicting results.
Two studies did identify neural stem cells, but the third failed to detect neurogenic populations. Have these new approaches, once again, failed to conclusively resolve the controversy regarding the existence of hippocampal regeneration in humans? Can you reconcile seemingly conflicting views and findings?
technical problem
In this study, researchers critically discussed and re-analyzed previously published single-cell transcriptomics datasets. They caution that the design, analysis, and interpretation of these studies in the adult hippocampus can be confounded by certain issues that call for conceptual, methodological, and computational adjustments.
A set of specific challenges was explored by reanalyzing previously published datasets. These deserve special attention and would greatly benefit from open discussion on the ground.
Giorgia Tosoni: ‘Analyzing previously published single-cell transcriptomic studies and conducting a meta-analysis to ensure that adult neurogenic populations differ across species, particularly when comparing mice and humans.’ We evaluated whether it could be identified.
“Neurogenerative processes in the adult mouse are very well characterized and the profiles of the different cell populations involved are known. These actually identify neurogenic cells in the human brain. It is the same molecular and cellular signature that has been widely used in the field for
“However, due to some evolutionary adaptations, mouse and human neurogenesis are expected to differ. I was.
“We found very little, if any, overlap between the two, which suggests that the mouse putative markers that we have been using for so long may not be suitable for the human brain. We also found that such a study would require significant statistical power: if neuronal regeneration occurs in the adult brain, it is expected to be extremely rare. Therefore, sufficient numbers of cells must be sequenced to identify these rare and possibly neurogenic populations.
“Other parameters are also important, such as sample quality. The interval between donor death and downstream processing is important as tissue quality and resulting data quality declines over time.
Reproducibility is key
Dilara Ayyildiz: “These new techniques, if applied appropriately, map hippocampal regeneration in the human brain and may be best suited for therapeutic intervention in aging, neurodegenerative and neuropsychiatric disorders.” It offers a unique opportunity to explore species and conditions. However, reproducibility and consistency are key.
During our analysis, we realized that seemingly small, but very important details and parameters of the experimental and computational pipeline can have a large impact on the results and influence the interpretation of the data. I noticed.
“Accurate reporting is essential to make these single-cell transcriptomics experiments and their analysis reproducible. Applying common computational pipelines and criteria to re-analyze these previous studies , realized that the apparent controversy in this area may actually be misleading. Our research suggests that there may actually be more agreement than previously believed. I propose
Summary prepared with assistance from Chat GPT AI technology
About this neuroscience research news
author: press office
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contact: Press Office – KNAW
image: image is public domain
Original research: open access.
“Mapping Human Adult Hippocampal Neurogenesis by Single-Cell Transcriptomics: Settling Controversy or Fueling Controversy?” by Giorgia Tosoni et al. neuron
overview
Mapping Human Adult Hippocampal Neurogenesis by Single-Cell Transcriptomics: Settling Controversy or Fueling Controversy?
highlight
- Single-cell profiling of adult hippocampal neurogenesis can provide important insights
- Methodological and conceptual confounding factors can influence the resulting dataset
- Sample size and stratification, data processing, and marker selection are critical
- Efforts should focus on protocol and pipeline optimization and public sharing
summary
The concept of harnessing the regenerative capacity of the human brain in physiological aging or neurological disease is a particularly attractive alternative to traditional strategies for enhancing or restoring brain function. But the first major question to tackle is whether the human brain has the capacity to regenerate.
The existence of human adult hippocampal neurogenesis (AHN) has been at the center of intense scientific debate for many years. The emergence of single-cell transcriptome technology was initially viewed as a panacea for resolving this controversy. However, recent single-cell RNA-sequencing studies in the human hippocampus yielded conflicting results.
Here, we critically discuss and reanalyze previously published AHN-associated single-cell transcriptome datasets.
Although promising, single-cell transcriptome profiling of AHN in the human brain presents methodological, conceptual, and biological implications that need to be addressed consistently across studies and openly debated within the scientific community. I argue that it can be confusing depending on the factors.
