Biology subjects

Spatz, A.

Publications and source records attributed to Spatz, A..

3 recordsLinked to original sources

bioRxiv2025

Characterizing Oligodendrocyte-Lineage Cells and Myelination in the Basolateral Amygdala: Insights from a Novel Methodology in Postmortem Human Brain

The basolateral amygdala (BLA) plays a key role in the pathophysiology of depressive disorders and trauma, yet oligodendrocyte-lineage cells and myelin in this brain region remain understudied in humans. This may be due, at least in part, to the lack of a cost-effective, antibody-based method to isolate oligodendrocytes (OL) and OL precursor cells (OPC) from postmortem brain tissue that is compatible with molecular biology applications. This study aimed to 1) create and validate a method for isolating OPC and OL nuclei from frozen postmortem grey matter; 2) compare OPC and OL gene expression in the BLA between individuals with depression who died by suicide (with or without a history of childhood abuse) and matched controls; and 3) provide histological characterizations of OPC, OL, and myelin in the BLA. Frozen left-hemisphere BLA samples were obtained from brain donors with well-characterized phenotypic information. Immunolabeled nuclei were sorted into OPC (SOX10+/CRYAB-) and OL (SOX10+/CRYAB+) populations, and RNA was measured using a custom Nanostring codeset. Fluorescence in situ hybridization was used to determine OPC (PDGFR+) and OL (MYRF+) densities, and immunofluorescence was used to label axons (NF-H) and myelin (MBP) for myelin area fraction. The method successfully isolated OPC and OL nuclei with correct transcriptomic profiles. In the OL fraction, MOBP was found to be significantly decreased in depressed individuals with a history of child abuse compared to controls, but no other genes showed significant group differences in either fraction. However, significant age-related patterns were observed in both fractions. Furthermore, no significant differences in cell densities or myelin coverage were observed across groups. Lastly, a strong significant correlation between OL density and myelin area fraction was identified. This study provides a novel sorting method and a comprehensive characterization of OL-lineage gene expression, cell densities, and myelin in the human BLA.

neuroscience↗

bioRxiv2022

ATAC-Seq and RNA-Seq combined analysis elucidates the impact of BORIS/CTCFL on melanoma progression, mediated by chromatin accessibility and gene expression alterations

Melanoma is the deadliest form of skin cancer, due to its tendency to metastasize early. Brother of Regulator of Imprinted Sites (BORIS), also known as CCCTC binding factor-Like (CTCFL), is a transcription regulator that becomes ectopically expressed in melanoma. We recently showed that BORIS contributes to melanoma phenotype switching by altering the gene expression program of proliferative melanoma cells in favor of a more invasive phenotype. However, how BORIS alters the transcriptome remains unclear. Here, ATAC-seq was used to study BORIS-mediated chromatin accessibility alterations in proliferative melanoma cells. Genes that gained promoter accessibility following ectopic BORIS expression, were enriched for melanoma-specific invasive genes as well as invasion-associated biological processes, while promoters of genes associated with proliferation show reduce accessibility. Integration of ATAC-Seq and RNA-Seq data demonstrates that increased chromatin accessibility is associated with transcriptional upregulation of genes involved in tumor progression processes, and the aberrant activation of oncogenic transcription factors, while reduced chromatin accessibility and downregulated genes, were associated with repressed activity of tumor suppressors. Together, these findings indicate that BORIS mediates transcriptional reprogramming in melanoma cells by altering chromatin accessibility and gene expression, shifting the cellular transcription landscape of proliferative melanoma cells towards a pro-invasive genetic signature. SignificanceWe recently reported that BORIS contributes to melanoma phenotype switching by altering the transcriptional landscape of melanoma cells from a proliferative to an invasive state. In this study, using ATAC-Seq, we demonstrate that ectopic BORIS expression in proliferative melanoma cells leads to increased chromatin accessibility at promoters of upregulated invasion-associated genes. Importantly, by integrating the ATAC-Seq data with RNA-Seq data, we were able to identify key cancer-associated transcription factors that become aberrantly activated or repressed following ectopic BORIS expression. Taken together, this study sheds light on the mechanisms by which BORIS mediates phenotype switching in melanoma cells.

cancer biology↗

bioRxiv2019

BORIS/CTCFL promotes a switch from a proliferative towards an invasive phenotype in melanoma cell lines

Melanoma is among the most aggressive cancers due to its tendency to metastasize early. Phenotype switching between a proliferative and an invasive state has been suggested as a critical process for metastasis. The mechanisms that regulate these transitions are poorly understood, but are associated with transcriptional changes. Brother of Regulator of Imprinted Sites (BORIS), also known as CCCTC binding factor-Like (CTCFL), is a transcriptional modulator that becomes aberrantly expressed in melanoma. Here, we provide the first evidence that BORIS is involved in phenotype switching in melanoma. Genetic modification of BORIS expression in melanoma cells combined with whole transcriptome analysis indicated that BORIS expression contributes to an invasion-associated transcriptome. In agreement with this finding, inducible BORIS overexpression in melanoma cells reduced proliferation and increased migration and invasion, demonstrating that the transcriptional switch is accompanied by a phenotypic switch. Overall, our study indicates a pro-invasive role for BORIS in melanoma via transcriptional reprogramming.

cancer biology↗