Generation of human induced pluripotential stem cells from individuals with complex heterozygous, isogenic corrected, and homozygous Bloc1s1 mutations

Kaiyuan Wu; Asako Takanohashi; Sarah Woidill; Allen Seylani; Guy Helman; Patricia Dias; Jeanette Beers; Yongshun Lin; Cas Simons; Ernst Wolvetang; Jizhong Zou; Adeline Vanderver; Michael N. Sack

Stem Cell Research (Oct 2022)

Generation of human induced pluripotential stem cells from individuals with complex heterozygous, isogenic corrected, and homozygous Bloc1s1 mutations

Kaiyuan Wu,
Asako Takanohashi,
Sarah Woidill,
Allen Seylani,
Guy Helman,
Patricia Dias,
Jeanette Beers,
Yongshun Lin,
Cas Simons,
Ernst Wolvetang,
Jizhong Zou,
Adeline Vanderver,
Michael N. Sack

Affiliations

Kaiyuan Wu: Laboratory of Mitochondrial Biology and Metabolism, National Heart Lung and Blood Institute, Bethesda, MD, USA
Asako Takanohashi: Division of Neurology, Children’s Hospital of Philadelphia, Philadelphia, PA, USA
Sarah Woidill: Division of Neurology, Children’s Hospital of Philadelphia, Philadelphia, PA, USA
Allen Seylani: Laboratory of Mitochondrial Biology and Metabolism, National Heart Lung and Blood Institute, Bethesda, MD, USA
Guy Helman: Division of Neurology, Children’s Hospital of Philadelphia, Philadelphia, PA, USA
Patricia Dias: Centro Hospitalar Universitario Lisboa Norte, E.P.E, Portugal
Jeanette Beers: iPSC Core, National Heart Lung and Blood Institute, Bethesda, MD, USA
Yongshun Lin: iPSC Core, National Heart Lung and Blood Institute, Bethesda, MD, USA
Cas Simons: Murdoch Children’s Research Institute, Royal Children’s Hospital, Melbourne, Victoria, Australia
Ernst Wolvetang: Australian Institute for Bioengineering and Nanotechnology, University of Queensland, Brisbane, Australia
Jizhong Zou: iPSC Core, National Heart Lung and Blood Institute, Bethesda, MD, USA
Adeline Vanderver: Division of Neurology, Children’s Hospital of Philadelphia, Philadelphia, PA, USA; Department of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
Michael N. Sack: Laboratory of Mitochondrial Biology and Metabolism, National Heart Lung and Blood Institute, Bethesda, MD, USA; Corresponding author.

Journal volume & issue: Vol. 64
p. 102905

Abstract

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Genetic studies show that BLOC1S1 modulates mitochondrial and endosome-lysosome function (Wu et al., 2021a). Furthermore, Bloc1s1 mutations are linked to leukodystrophy (Bertoli-Avella et al., 2021). The Vanderver laboratory identified additional individuals with leukodystrophy that harbored either complex heterozygous (Bloc1s1 c.206A > C and c.359G > A), or homozygous (Bloc1s1 c.185 T > C) point mutations. We generated induced pluripotential stem cell (iPSC) lines from these subjects, from parents of the complex heterozygous mutations patient, and from CRISPR isogenic (c.206A > C and c.359G > A) corrected iPSC-line. These complex heterozygous, homozygous, and isogenic-corrected Bloc1s1 lines were phenotypically normal and were capable of differentiation towards the three germ layers.

Published in Stem Cell Research

ISSN: 1873-5061 (Print); 1876-7753 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Science: Biology (General)
Website: https://www.journals.elsevier.com/stem-cell-research

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