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6. Extracellular Vesicles in Serum and Central Nervous System Tissues Contain microRNA Signatures in Sporadic Amyotrophic Lateral Sclerosis

Author

Lo, Ting-wen, primary, Figueroa-Romero, Claudia, additional, Hur, Junguk, additional, Pacut, Crystal, additional, Stoll, Evan, additional, Spring, Calvin, additional, Lewis, Rose, additional, Nair, Athul, additional, Goutman, Stephen A., additional, Sakowski, Stacey A., additional, Nagrath, Sunitha, additional, and Feldman, Eva L., additional

Published
2021
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8. Magnetic resonance imaging of human neural stem cells in rodent and primate brain

Author

McGinley, Lisa M., primary, Willsey, Matthew S., additional, Kashlan, Osama N., additional, Chen, Kevin S., additional, Hayes, John M., additional, Bergin, Ingrid L., additional, Mason, Shayna N., additional, Stebbins, Aaron W., additional, Kwentus, Jacquelin F., additional, Pacut, Crystal, additional, Kollmer, Jennifer, additional, Sakowski, Stacey A., additional, Bell, Caleb B., additional, Chestek, Cynthia A., additional, Murphy, Geoffrey G., additional, Patil, Parag G., additional, and Feldman, Eva L., additional

Published
2020
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9. Additional file 1 of Genome-wide profiling of DNA methylation and gene expression identifies candidate genes for human diabetic neuropathy

Author

Guo, Kai, Eid, Stephanie A., Elzinga, Sarah E., Pacut, Crystal, Feldman, Eva L., and Hur, Junguk

Abstract

Additional file 1: Figure S1. Sample distribution based on transcriptomic data. Figure S2. MA plot showing the top 50 DEGs in Group 1 versus Group 2. Figure S3. Gene expression patterns of the most significant 100 DEGs between Group 1 and Group 2. Figure S4. Functional enrichment analysis of DEGs by Reactome and DO. Figure S5. Functional enrichment analysis of DMGs by Reactome and DO. Figure S6. Functional enrichment analysis of overlapping DEGs and DMGs in the same direction.

Published
2020
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14. RNA-SEQ analysis of human diabetic neuropathy in subjects with type 2 diabetes

Author

Guo, Kai, de Anda-Jauregui, Guillermo, McGregor, Brett A., Backus, Carey, Pacut, Crystal, Feldman, Eva L., and Hur, Junguk

Subjects
Type 2 diabetes -- Complications and side effects -- Genetic aspects, RNA sequencing -- Methods, Diabetic neuropathies -- Genetic aspects, Science and technology
Abstract

Diabetic neuropathy (DN) is one of the most common complications of diabetes mellitus (DM). Based on our previous results we identified HbA1c as the sole significantly associated clinical factor with myelinated fiber density change(%delta-MFD). Here, we performed a RNA-Seq profiling on 78 sural nerves from DN patients with type 2 diabetes (T2DM). We performed unbiased clustering analyses on the RNA-Seq gene expression data and identified three distinctive groups of samples. Multifactorial logistic regression analyses on the clinical data of these groups identified that these groups were significantly different in terms of baseline HbAlc level and O'Brien neuropathy score. 997 differentially expressed genes were identified between Group1 and Group2, respectively with the highest and lowest average HbA1c levels. Functional enrichment analysis in terms of Gene Ontology terms and KEGG pathways reveals that these DEGs were highly enriched with genes related to extracellular matrix organization, phagosome, antigen processing and presentation pathway as well as adaptive immune system. In conclusion, a deep-sequencing analysis of the peripheral nerves affected by T2DM revealed that the global gene expression patterns in these samples did not correlate with %delta-MFD. However, they were significantly associated with the baseline HbA1c and O'Brien neuropathy score, suggesting their critical roles in driving gene expression changes in peripheral nerves in T2DM., Kai Guo * (P1), Guillermo de Anda-Jauregui (1), Brett A McGregor (1), Carey Backus (2), Crystal Pacut (2), Eva L Feldman (2), and Junguk Hur (1) (1) Department of Biomedical [...]

Published
2017

18. Autocrine Production of IGF‐IIncreases Stem Cell‐Mediated Neuroprotection

Author

Lunn, J. Simon, Sakowski, Stacey A., McGinley, Lisa M., Pacut, Crystal, Hazel, Thomas G., Johe, Karl, and Feldman, Eva L.

Abstract

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder resulting in motor neuron (MN) loss. There are currently no effective therapies; however, cellular therapies using neural progenitor cells protect MNs and attenuate disease progression in G93A‐SOD1 ALS rats. Recently, we completed a phase I clinical trial examining intraspinal human spinal stem cell (HSSC) transplantation in ALS patients which demonstrated our approach was safe and feasible, supporting the phase II trial currently in progress. In parallel, efforts focused on understanding the mechanisms underlying the preclinical benefit of HSSCs in vitro and in animal models of ALS led us to investigate how insulin‐like growth factor‐I (IGF‐I) production contributes to cellular therapy neuroprotection. IGF‐I is a potent growth factor with proven efficacy in preclinical ALS studies, and we contend that autocrine IGF‐I production may enhance the salutary effects of HSSCs. By comparing the biological properties of HSSCs to HSSCs expressing sixfold higher levels of IGF‐I, we demonstrate that IGF‐I production augments the production of glial‐derived neurotrophic factor and accelerates neurite outgrowth without adversely affecting HSSC proliferation or terminal differentiation. Furthermore, we demonstrate that increased IGF‐I induces more potent MN protection from excitotoxicity via both indirect and direct mechanisms, as demonstrated using hanging inserts with primary MNs or by culturing with organotypic spinal cord slices, respectively. These findings support our theory that combining autocrine growth factor production with HSSC transplantation may offer a novel means to achieve additive neuroprotection in ALS. StemCells2015;33:1480–1489

Published
2015
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