Single-cell epigenomics and spatiotemporal transcriptomics reveal human cerebellar development.

Human cerebellar development is orchestrated by molecular regulatory networks to achieve cytoarchitecture and coordinate motor and cognitive functions. Here, we combined single-cell transcriptomics, spatial transcriptomics and single cell chromatin accessibility states to systematically depict an integrative spatiotemporal landscape of human fetal cerebellar development. We revealed that combinations of transcription factors and cis-regulatory elements (CREs) play roles in governing progenitor differentiation and cell fate determination along trajectories in a hierarchical manner, providing a gene expression regulatory map of cell fate and spatial information for these cells. We also illustrated that granule cells located in different regions of the cerebellar cortex showed distinct molecular signatures regulated by different signals during development. Finally, we mapped single-nucleotide polymorphisms (SNPs) of disorders related to cerebellar dysfunction and discovered that several disorder-associated genes showed spatiotemporal and cell type-specific expression patterns only in humans, indicating the cellular basis and possible mechanisms of the pathogenesis of neuropsychiatric disorders.

The single-cell and spatial transcriptional landscape of human gastrulation and early brain development.

The emergence of the three germ layers and the lineage-specific precursor cells orchestrating organogenesis represent fundamental milestones during early embryonic development. We analyzed the transcriptional profiles of over 400,000 cells from 14 human samples collected from post-conceptional weeks (PCW) 3 to 12 to delineate the dynamic molecular and cellular landscape of early gastrulation and nervous system development. We described the diversification of cell types, the spatial patterning of neural tube cells, and the signaling pathways likely involved in transforming epiblast cells into neuroepithelial cells and then into radial glia. We resolved 24 clusters of radial glial cells along the neural tube and outlined differentiation trajectories for the main classes of neurons. Lastly, we identified conserved and distinctive features across species by comparing early embryonic single-cell transcriptomic profiles between humans and mice. This comprehensive atlas sheds light on the molecular mechanisms underlying gastrulation and early human brain development.

Mouse and human share conserved transcriptional programs for interneuron development.

Genetic variation confers susceptibility to neurodevelopmental disorders by affecting the development of specific cell types. Changes in cortical and striatal γ-aminobutyric acid­expressing (GABAergic) neurons are common in autism and schizophrenia. In this study, we used single-cell RNA sequencing to characterize the emergence of cell diversity in the human ganglionic eminences, the transitory structures of the human fetal brain where striatal and cortical GABAergic neurons are generated. We identified regional and temporal diversity among progenitor cells underlying the generation of a variety of projection neurons and interneurons. We found that these cells are specified within the human ganglionic eminences by transcriptional programs similar to those previously identified in rodents. Our findings reveal an evolutionarily conserved regulatory logic controlling the specification, migration, and differentiation of GABAergic neurons in the human telencephalon.

Interrogation of the microenvironmental landscape in spinal ependymomas reveals dual functions of tumor-associated macrophages.

Spinal ependymomas are the most common spinal cord tumors in adults, but their intratumoral cellular heterogeneity has been less studied, and how spinal microglia are involved in tumor progression is still unknown. Here, our single-cell RNA-sequencing analyses of three spinal ependymoma subtypes dissect the microenvironmental landscape of spinal ependymomas and reveal tumor-associated macrophage (TAM) subsets with distinct functional phenotypes. CCL2+ TAMs are related to the immune response and exhibit a high capacity for apoptosis, while CD44+ TAMs are associated with tumor angiogenesis. By combining these results with those of single-cell ATAC-sequencing data analysis, we reveal that TEAD1 and EGR3 play roles in regulating the functional diversity of TAMs. We further identify diverse characteristics of both malignant cells and TAMs that might underlie the different malignant degrees of each subtype. Finally, assessment of cell-cell interactions reveal that stromal cells act as extracellular factors that mediate TAM diversity. Overall, our results reveal dual functions of TAMs in tumor progression, providing valuable insights for TAM-targeting immunotherapy.

Psychometric Properties of a Simplified Chinese Version of the Secondary Trauma Questionnaire in a Potentially Traumatized Study Sample.

BACKGROUND: Screening for secondary traumatic stress (STS) is lacking in China. It is unclear whether Western models of STS can be adapted satisfactorily for use in non-Western regions. The 20-item Secondary Trauma Questionnaire (STQ) is a self-report measure of traumatic stress symptoms in individuals who have been influenced indirectly by suicide or violent injury of people important to the respondents. METHODS: Here, we assessed the psychometric properties of a newly developed Chinese version of the STQ in a potentially traumatized sample (N = 875) composed of doctors, nurses, teachers, civic administration staff, and social workers in China. We performed reliability and validity analyses. Subsequently, we split the total sample into two subsamples for exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) for measurement invariance analyses. RESULTS: The full scale demonstrated good internal consistency (Cronbach's α = 0.95-0.97), convergent validity, discriminant validity, and factorial validity. CFA affirmed a one-factor structure; the configural, metric, scalar, and strict invariances of the STQ were acceptable across genders. CONCLUSION: The present results indicate that the STQ is a reliable and valid self-report assessment for use with potentially traumatized people in China, and further supports the notion that the STQ is amenable to additional future cross-cultural adaptation.

Effect of Positive Psychological Intervention on Posttraumatic Growth among Primary Healthcare Workers in China: A Preliminary Prospective Study.

Posttraumatic growth (PTG) is defined as positive psychological change in the wake of highly challenging circumstances. Healthcare workers in particular are more vulnerable to stressors and trauma than the general population. The current study examined the use and effectiveness of a novel positive psychological intervention based on Chinese traditional culture to improve PTG in hospital healthcare workers. The intervention was provided to 579 healthcare workers at hospitals in Guilin, Shenzhen and Xiangtan. Scores on the Posttraumatic Growth Inventory (PTGI) and its subscales were significantly higher after intervention than before (p < 0.001). Of the five aspects of PTG, the aspect of "new possibilities" benefited the most from intervention (Cohen's d = 0.45). PTG in women, nurses and college graduates increased to a greater extent than other participants after intervention. It was concluded that our novel intervention is effective at improving PTG in medical staff.