A stress-free strategy to correct point mutations in patient iPS cells

Cai, Jingli; Kropf, Elizabeth; Hou, Ya‐Ming; Iacovitti, Lorraine

doi:10.1016/j.scr.2021.102332

Cited by 5 publications

(3 citation statements)

References 14 publications

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“…Thus, in collaborative experiments where iPSCs from C9orf72-ALS patients were differentiated into spinal motor neurons and used to study ALS pathogenic mechanisms, the Trotti/Passinelli laboratory showed evidence of cell-to-cell spread of potentially disease-causing dipeptide repeat proteins (Westergard et al, 2016). More recently, in a collaboration with Jefferson colleagues studying Charcot-Marie-Tooth disease, we developed a new gene editing approach to correct the disease mutation in iPSCs generated from Charcot-Marie-Tooth patients (Cai et al, 2021).…”

Section: Ipscs In Disease Modelingmentioning

confidence: 99%

“…In grafts, the presence of heterogeneous cell types (including potentially excitotoxic glutamatergic neurons) poses a major stumbling block in moving stem cells to the clinic. Thus, we are currently working on the generation of Lmx1a, En1, Pitx3, and TH reporter iPSC lines using new advances in gene editing methodologies (Cai et al, 2021). These reporter lines will hopefully address the vexing issue of cell heterogeneity by allowing us to FACS purify midbrain dopamine progenitors and midbrain dopamine neurons for PD modeling in culture.…”

Section: Going Forwardmentioning

confidence: 99%

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On the Road from Phenotypic Plasticity to Stem Cell Therapy

Iacovitti

2021

J. Neurosci.

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In 1981, I published a paper in the first issue of The Journal of Neuroscience with my postdoctoral mentor, Richard Bunge. At that time, the long-standing belief that each neuron expressed only one neurotransmitter, known as Dale's Principle (Dale, 1935), was being hotly debated following a report by French embryologist Nicole Le Douarin showing that neural crest cells destined for one transmitter phenotype could express characteristics of another if transplanted to alternate sites in the developing embryo (Le Douarin, 1980). In the Bunge laboratory, we were able to more directly test the question of phenotypic plasticity in the controlled environment of the tissue culture dish. Thus, in our paper, we grew autonomic catecholaminergic neurons in culture under conditions which promoted the acquisition of cholinergic traits and showed that cells did not abandon their inherited phenotype to adopt a new one but instead were capable of dual transmitter expression. In this Progressions article, I detail the path that led to these findings and how this study impacted the direction I followed for the next 40 years. This is my journey from phenotypic plasticity to the promise of a stem cell therapy.

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Section: Ipscs In Disease Modelingmentioning

confidence: 99%

Section: Going Forwardmentioning

confidence: 99%

On the Road from Phenotypic Plasticity to Stem Cell Therapy

Iacovitti

2021

J. Neurosci.

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“…Several other scarless editing approaches have been described but all have limitations. Two-step editing using large cassettes that are later excised 6 – 8 is promising but involves transfection of large amounts of DNA that can be toxic to the cells and can be laborious to assemble, especially if one wants to follow identical procedures for both alleles. Base editing can be problematic due to undesired editing of other nearby bases and restriction to specific modifications 9 .…”

mentioning

confidence: 99%