NetREm: Network Regression Embeddings reveal cell-type transcription factor coordination for gene regulation.

Motivation: Transcription factor (TF) coordination plays a key role in gene regulation via direct and/or indirect protein-protein interactions (PPIs) and co-binding to regulatory elements on DNA. Single-cell technologies facilitate gene expression measurement for individual cells and cell-type identification, yet the connection between TF-TF coordination and target gene (TG) regulation of various cell types remains unclear.

Results: To address this, we introduce our innovative computational approach, Network Regression Embeddings (NetREm), to reveal cell-type TF-TF coordination activities for TG regulation.

TFEB/3 Govern Repair Schwann Cell Generation and Function Following Peripheral Nerve Injury.

TFEB and TFE3 (TFEB/3), key regulators of lysosomal biogenesis and autophagy, play diverse roles depending on cell type. This study highlights a hitherto unrecognized role of TFEB/3 crucial for peripheral nerve repair. Specifically, they promote the generation of progenitor-like repair Schwann cells after axonal injury.

NetREm: Network Regression Embeddings reveal cell-type transcription factor coordination for gene regulation.

Transcription factor (TF) coordination plays a key role in target gene (TG) regulation via protein-protein interactions (PPIs) and DNA co-binding to regulatory elements. Single-cell technologies facilitate gene expression measurement for individual cells and cell-type identification, yet the connection between TF coordination and TG regulation of various cell types remains unclear. To address this, we have developed a novel computational approach, Network Regression Embeddings (NetREm), to reveal cell-type TF-TF coordination activities for TG regulation.

Modulation of Schwann cell homeostasis by the BAP1 deubiquitinase.

Schwann cell programming during myelination involves transcriptional networks that activate gene expression but also repress genes that are active in neural crest/embryonic differentiation of Schwann cells. We previously found that a Schwann cell-specific deletion of the EED subunit of the Polycomb Repressive Complex (PRC2) led to inappropriate activation of many such genes. Moreover, some of these genes become re-activated in the pro-regenerative response of Schwann cells to nerve injury, and we found premature activation of the nerve injury program in a Schwann cell-specific knockout of Eed.

JUN Regulation of Injury-Induced Enhancers in Schwann Cells.

Schwann cells play a critical role after peripheral nerve injury by clearing myelin debris, forming axon-guiding bands of Büngner, and remyelinating regenerating axons. Schwann cells undergo epigenomic remodeling to differentiate into a repair state that expresses unique genes, some of which are not expressed at other stages of Schwann cell development. We previously identified a set of enhancers that are activated in Schwann cells after nerve injury, and we determined whether these enhancers are preprogrammed into the Schwann cell epigenome as poised enhancers before injury.

H3K27 demethylases are dispensable for activation of Polycomb-regulated injury response genes in peripheral nerve.

The induction of nerve injury response genes in Schwann cells depends on both transcriptional and epigenomic reprogramming. The nerve injury response program is regulated by the repressive histone mark H3K27 trimethylation (H3K27me3), deposited by Polycomb repressive complex 2 (PRC2). Loss of PRC2 function leads to early and augmented induction of the injury response gene network in peripheral nerves, suggesting H3K27 demethylases are required for derepression of Polycomb-regulated nerve injury genes.

Schwann cell transcript biomarkers for hereditary neuropathy skin biopsies.

Objective: Charcot-Marie-Tooth (CMT) disease is most commonly caused by duplication of a chromosomal segment surrounding Peripheral Myelin Protein 22, or PMP22 gene, which is classified as CMT1A. Several candidate therapies reduce Pmp22 mRNA levels in CMT1A rodent models, but development of biomarkers for clinical trials in CMT1A is a challenge given its slow progression and difficulty in obtaining nerve samples. Quantitative PCR measurements of PMP22 mRNA in dermal nerves were performed using skin biopsies in human clinical trials for CMT1A, but this approach did not show increased PMP22 mRNA in CMT1A patients compared to controls.

Functional and radiological outcomes of operative management of displaced talar neck fractures.

Aim: To evaluate functional and radiological results of internal fixation of displaced talar neck fractures.

Materials And Methods: Twenty patients with displaced talar neck fractures who underwent surgery and fixation by cancellous screws were evaluated. Patients were evaluated by American Orthopedic Foot and Ankle Society score which is based on pain (40 points), function (50 points) and alignment (10 points) with excellent (90-100 points), good (75-89 points), fair (60-74 points) and poor scores (<60 points) and radiographically for assessment of union, osteonecrosis and osteoarthritic changes in the subtalar and ankle joint.