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

doi:10.1016/j.scr.2022.102905

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

Stem Cell Res. 2022 Oct:64:102905. doi: 10.1016/j.scr.2022.102905. Epub 2022 Aug 30.

Authors

Affiliations

¹ Laboratory of Mitochondrial Biology and Metabolism, National Heart Lung and Blood Institute, Bethesda, MD, USA.
² Division of Neurology, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
³ Centro Hospitalar Universitario Lisboa Norte, E.P.E, Portugal.
⁴ iPSC Core, National Heart Lung and Blood Institute, Bethesda, MD, USA.
⁵ Murdoch Children's Research Institute, Royal Children's Hospital, Melbourne, Victoria, Australia.
⁶ Australian Institute for Bioengineering and Nanotechnology, University of Queensland, Brisbane, Australia.
⁷ Division of Neurology, Children's Hospital of Philadelphia, Philadelphia, PA, USA; Department of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
⁸ Laboratory of Mitochondrial Biology and Metabolism, National Heart Lung and Blood Institute, Bethesda, MD, USA. Electronic address: sackm@nhlbi.nih.gov.

PMID: 36070637
DOI: 10.1016/j.scr.2022.102905

Abstract

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 by Elsevier B.V.

Publication types

Research Support, Non-U.S. Gov't
Research Support, N.I.H., Intramural
Research Support, N.I.H., Extramural

MeSH terms

Clustered Regularly Interspaced Short Palindromic Repeats
Heterozygote
Homozygote
Humans
Induced Pluripotent Stem Cells* / metabolism
Mutation / genetics
Nerve Tissue Proteins / metabolism

Substances

BLOC1S1 protein, human
Nerve Tissue Proteins

Abstract

Publication types

MeSH terms

Substances

Grants and funding