Mapping human adult hippocampal neurogenesis with single-cell transcriptomics: Reconciling controversy or fueling the debate?

The notion of exploiting the regenerative potential of the human brain in physiological aging or neurological diseases represents a particularly attractive alternative to conventional strategies for enhancing or restoring brain function. However, a major first question to address is whether the human brain does possess the ability to regenerate. The existence of human adult hippocampal neurogenesis (AHN) has been at the center of a fierce scientific debate for many years. The advent of single-cell transcriptomic technologies was initially viewed as a panacea to resolving this controversy. However, recent single-cell RNA sequencing studies in the human hippocampus yielded conflicting results. Here, we critically discuss and re-analyze previously published AHN-related single-cell transcriptomic datasets. We argue that, although promising, the single -cell transcriptomic profiling of AHN in the human brain can be confounded by methodological, conceptual, and biological factors that need to be consistently addressed across studies and openly discussed within the scientific community.

Automated summary

The potential of exploiting the regenerative capacity of the human brain has gained attention as an alternative strategy for enhancing or restoring brain function in physiological aging or neurological diseases. However, there is a debate regarding whether the human brain has the ability to regenerate. Recent single-cell RNA sequencing studies in the human hippocampus have yielded conflicting results, raising concerns about the reliability of this approach. In this article, we critically discuss and re-analyze previously published single-cell transcriptomic datasets related to human adult hippocampal neurogenesis (AHN), highlighting the importance of addressing methodological, conceptual, and biological factors in studying AHN.