Tracing Human Brain Development from Conception to Adulthood via Single-Cell Study
Summary
The development of the human brain is characterized by ongoing changes at the molecular and cellular levels that continue into the third decade of life. In order to understand the cell processes that drive neural maturation, they analyzed gene expression and chromatin accessibility in the prefrontal cortex at the single-cell level from gestation to adulthood. Through integrative analyses, they were able to identify the changing patterns of gene expression in each cell type and understand how these changes are regulated. They also observed a major shift in gene expression during the transition from prenatal to postnatal development in all cell types, and continued changes into adulthood. In addition, they found connections between gene expression dynamics and developmental milestones and identified the different times at which cells reach adult-like states. Furthermore, they discovered molecular pathways involved in neurological disorders. Finally, using this data as a reference, they evaluated the maturation of cell identities in organoid models. Overall, this work provides insights into the complex regulatory landscape of human cortical development.
Fig.1 Graphical abstract. (Herring, 2022)
Research Criteria
This study characterizes the changes in gene expression and chromatin accessibility that occur during the development of the human prefrontal cortex (PFC) at the single-cell level, from gestation to adulthood. This allows for the analysis of active pathways and their dynamics in various cell types in the cortex throughout development, as well as the specific timing of maturation for each cell type. It also allows for the identification of the cis-regulatory logic and associated factors that control these processes, aiding in the molecular understanding of neural cell development.
Fig.2 Schematic of developmental stages, sample ages, brain region, profiling methods, and libraries generated in this study. (Herring, 2022)
Sample Type
Nuclei isolation from human PFC samples from neurotypical individuals of various ages from mid-gestation through adulthood and one individual with ASD (autism spectrum disorder).
Result—A Single Nuclei Resolution Transcriptome Reference of Human Brain Development
The researchers performed single nuclei RNA-seq (snRNA-seq) profiling on 26 postmortem samples of the prefrontal cortex (PFC) from individuals at various stages of development, including fetal, neonatal, infancy, childhood, adolescence, and adulthood. They generated 154,748 single nuclei transcriptome profiles after quality filtering and created a developmental reference with the distinct chronological ordering of all major neural lineages. They identified 86 distinct clusters across all developmental stages and annotated them by dividing nuclei into either excitatory principal neurons (PNs), inhibitory interneurons (INs), or glia, and further separating the major clusters using layer and subtype-specific marker genes.
Fig.3 A single nuclei resolution transcriptome reference of human PFC development. (Herring, 2022)
Result—A Single Nuclei Resolution Chromatin Accessibility Map of Human PFC Development
To understand the cis-regulatory elements (CREs) that control the gene expression dynamics underlying the development of the prefrontal cortex (PFC), the researchers performed single nuclei chromatin accessibility profiling (snATAC-seq) on 17 postmortem PFC samples from the same developmental stages. They obtained chromatin accessibility data for 87,339 individual nuclei after quality filtering and grouped the data into 12 major cell states over development using label transfer from the snRNA-seq data. Using UMAP representation, they observed chronological ordering within neuronal cell types, indicating the progression of regulatory programs throughout development, and noted changes in the proportions of cell types with age.
Fig.4 Construction of a chromatin accessibility reference of the human PFC over development. (Herring, 2022)
Creative Biolabs' Services
Single Nuclei RNA Sequencing Service
Creative Biolabs offers a wide range of customized, high-quality single cell nuclei RNA sequencing services to support scientific research in biomedical industries worldwide, as well as a single-cell level research application platform for complex tissues like brain tissue, heart, kidney, or rare, cryopreserved samples, making tumor cell heterogeneity and pathogenic mechanisms easier to study.
Learn more
Single Cell ATAC Service
Creative Biolabs provides a comprehensive range of customized, high-quality services in single cell ATAC profiling to support various scientific research worldwide. Examining gene regulation at the single-cell level through the analysis of chromatin accessibility can provide insights into the underlying mechanisms.
Learn moreCreative Biolabs is a distinguished provider of advanced single cell analysis services, offering state-of-the-art single nuclei RNA sequencing and single cell ATAC (Assay for Transposase-Accessible Chromatin) sequencing services for researchers and organizations. Our cutting-edge technology and experienced team of scientists enable us to deliver high-quality data and insights for a wide range of applications, including basic research, drug development, and diagnostic testing.
The single nuclei RNA sequencing services offered by Creative Biolabs allow for the analysis of gene expression at the single nuclei level, providing a more detailed and accurate understanding of cellular diversity and function. Similarly, our single cell ATAC sequencing services provide a comprehensive view of the chromatin accessibility of individual cells, enabling the identification of regulatory elements and the understanding of cellular states. We are dedicated to providing our clients with the highest level of quality, accuracy, and services, ensuring that they receive the needed data and support to achieve their research goals. Creative Biolabs is honored to be a trustworthy partner for all your single-cell sequencing needs.
For any information, please contact us.
Reference
- Herring, C.A.; et al. Human prefrontal cortex gene regulatory dynamics from gestation to adulthood at single-cell resolution. Cell. 2022, 185(23): 4428-4447.
