Publications by authors named "Alvaro A Beltran"

5 Publications

  • Page 1 of 1

Pathogenic SPTBN1 variants cause an autosomal dominant neurodevelopmental syndrome.

Nat Genet 2021 Jul 1;53(7):1006-1021. Epub 2021 Jul 1.

McMaster University, Hamilton, Ontario, Canada.

SPTBN1 encodes βII-spectrin, the ubiquitously expressed β-spectrin that forms micrometer-scale networks associated with plasma membranes. Mice deficient in neuronal βII-spectrin have defects in cortical organization, developmental delay and behavioral deficiencies. These phenotypes, while less severe, are observed in haploinsufficient animals, suggesting that individuals carrying heterozygous SPTBN1 variants may also show measurable compromise of neural development and function. Here we identify heterozygous SPTBN1 variants in 29 individuals with developmental, language and motor delays; mild to severe intellectual disability; autistic features; seizures; behavioral and movement abnormalities; hypotonia; and variable dysmorphic facial features. We show that these SPTBN1 variants lead to effects that affect βII-spectrin stability, disrupt binding to key molecular partners, and disturb cytoskeleton organization and dynamics. Our studies define SPTBN1 variants as the genetic basis of a neurodevelopmental syndrome, expand the set of spectrinopathies affecting the brain and underscore the critical role of βII-spectrin in the central nervous system.
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http://dx.doi.org/10.1038/s41588-021-00886-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8273149PMC
July 2021

Generation of an induced pluripotent stem cell line (UNCCi002-A) from a healthy donor using a non-integration system to study Cerebral Cavernous Malformation (CCM).

Stem Cell Res 2021 Jul 9;54:102421. Epub 2021 Jun 9.

Human Pluripotent Stem Cell Core, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, United States; Department of Genetics at the University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, United States. Electronic address:

The generation of induced pluripotent stem cells (iPSCs) from healthy individuals is an invaluable resource as reference control in disease modeling and drug discovery. This paper details the reprogramming of peripheral blood mononuclear cells (PBMCs) isolated from a healthy 27 years-old male using non-integration technology. The derived iPSCs displayed typical pluripotent stem cell morphology, the capacity to differentiate into the three germ layers, and normal karyotype. This iPSC line will be used as a reference control to study the Cerebral Cavernous Malformation disease mechanism.
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http://dx.doi.org/10.1016/j.scr.2021.102421DOI Listing
July 2021

Segmentor: a tool for manual refinement of 3D microscopy annotations.

BMC Bioinformatics 2021 May 22;22(1):260. Epub 2021 May 22.

UNC Neuroscience Center, University of North Carolina at Chapel Hill, 116 Manning Drive, CB# 7250, Chapel Hill, NC, 27599, USA.

Background: Recent advances in tissue clearing techniques, combined with high-speed image acquisition through light sheet microscopy, enable rapid three-dimensional (3D) imaging of biological specimens, such as whole mouse brains, in a matter of hours. Quantitative analysis of such 3D images can help us understand how changes in brain structure lead to differences in behavior or cognition, but distinguishing densely packed features of interest, such as nuclei, from background can be challenging. Recent deep learning-based nuclear segmentation algorithms show great promise for automated segmentation, but require large numbers of accurate manually labeled nuclei as training data.

Results: We present Segmentor, an open-source tool for reliable, efficient, and user-friendly manual annotation and refinement of objects (e.g., nuclei) within 3D light sheet microscopy images. Segmentor employs a hybrid 2D-3D approach for visualizing and segmenting objects and contains features for automatic region splitting, designed specifically for streamlining the process of 3D segmentation of nuclei. We show that editing simultaneously in 2D and 3D using Segmentor significantly decreases time spent on manual annotations without affecting accuracy as compared to editing the same set of images with only 2D capabilities.

Conclusions: Segmentor is a tool for increased efficiency of manual annotation and refinement of 3D objects that can be used to train deep learning segmentation algorithms, and is available at https://www.nucleininja.org/ and https://github.com/RENCI/Segmentor .
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http://dx.doi.org/10.1186/s12859-021-04202-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8141214PMC
May 2021

Derivation of Induced Pluripotent Stem Cells from Human Fibroblasts Using a Non-integrative System in Feeder-free Conditions.

Bio Protoc 2020 Oct 20;10(20):e3788. Epub 2020 Oct 20.

Human Pluripotent Stem Cell Core, University of North Carolina, Chapel Hill, NC 27599, USA.

Induced pluripotent stem cells (iPSCs) are genetically reprogrammed somatic cells that exhibit features identical to those of embryonic stem cells (ESCs). Multiple approaches are available to derive iPSCs, among which the Sendai virus is the most effective at reprogramming different cell types. Here we describe a rapid, efficient, safe, and reliable approach to reprogram human fibroblasts into iPSCs that are compatible with future iPSCs uses such as genome editing and differentiation to a transplantable cell type.
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http://dx.doi.org/10.21769/BioProtoc.3788DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7842795PMC
October 2020

Generation of an integration-free induced pluripotent stem cell line (UNC001-A) from blood of a healthy individual.

Stem Cell Res 2020 12 1;49:102015. Epub 2020 Oct 1.

Human Pluripotent Stem Cell Core, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, United States; Department of Pharmacology at the University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, United States. Electronic address:

Induced pluripotent stem cells (iPSCs) generated from young, healthy individuals are valuable tools for investigating molecular disease mechanisms during the early development of the brain vasculature. We generated an iPSC line from peripheral blood mononuclear cells (PBMCs) isolated from a healthy 13-yeard old female donor using the Sendai virus. The iPSCs differentiated into endothelial cells, astrocytes, and neurons. This iPSC line can serve as a healthy reference control for comparative studies in drug development and modeling the early onset of Cerebral Cavernous Malformation (CCM).
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http://dx.doi.org/10.1016/j.scr.2020.102015DOI Listing
December 2020
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