RUES2 hESCs exhibit MGE-biased neuronal differentiation and muHTT-dependent defective specification hinting at SP1

Conforti, Paola; Besusso, Dario; Brocchetti, Silvia; Campus, Ilaria; Cappadona, Claudio; Galimberti, Maura; Laporta, Angela; Iennaco, Raffaele; Rossi, Riccardo L.; Bocchi, Vittoria Dickinson; Cattaneo, Elena

doi:10.1016/j.nbd.2020.105140

Cited by 5 publications

(6 citation statements)

References 83 publications

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“…Taking these studies under consideration, we modified the initial cell density 4 , 20 of 6 × 10 4 cells/cm 2 and plated H9 human embryonic stem (hES) cells at a density of 1 × 10 4 cells/cm 2 ( Figure 1 A). Lower densities cells do not form colonies and detach from the coating ( Figure S1 A).…”

Section: Resultsmentioning

confidence: 99%

“…We then tested the performance of an independent hES cell line (RUES2) that has been previously shown to be resistant to LGE differentiation and biased toward MGE fates. 20 , 22 Initial seed density of 6 × 10 4 in RUES2 showed that cells were not able to produce MSNs. 20 We therefore tested the same cell densities as used in the H9 lines.…”

Section: Resultsmentioning

confidence: 99%

“… 20 , 22 Initial seed density of 6 × 10 4 in RUES2 showed that cells were not able to produce MSNs. 20 We therefore tested the same cell densities as used in the H9 lines. We show that seeding at 1 × 10 4 cells/cm 2 is the optimal condition to form colonies after plating ( Figure S2 A) and is able to give 10% of CTIP2 + /DARPP32 + /GAD67 + cells by DIV40 ( Figures S2 B–S2D).…”

Section: Resultsmentioning

confidence: 99%

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In vitro-derived medium spiny neurons recapitulate human striatal development and complexity at single-cell resolution

Conforti

Bocchi

Campus

et al. 2022

Cell Reports Methods

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

In vitro-derived medium spiny neurons recapitulate human striatal development and complexity at single-cell resolution

Conforti

Bocchi

Campus

et al. 2022

Cell Reports Methods

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“…One allelic series was generated in the RUES2 line 153 using clustered regularly interspaced short palindromic repeats (CRISPR) technology and includes lines with 45, 50, 56–58, 67, and 72–74 CAG repeats 151 . These lines displayed developmental abnormalities 154 , such as yielding an increased number of progenitor cells 154 and forming aberrant rosettes 151 , 154 . Other novel phenotypes such as disruptions in cytokinesis and chromosomal instability 151 were detected, and changes in gene expression in developmental pathways previously detected in iPSCs were also found 151 , 154 .…”

Section: Isogenic Embryonic Stem Cell Lines To Study Cag Expansionsmentioning

confidence: 99%

“…These lines displayed developmental abnormalities 154 , such as yielding an increased number of progenitor cells 154 and forming aberrant rosettes 151 , 154 . Other novel phenotypes such as disruptions in cytokinesis and chromosomal instability 151 were detected, and changes in gene expression in developmental pathways previously detected in iPSCs were also found 151 , 154 .…”

Section: Isogenic Embryonic Stem Cell Lines To Study Cag Expansionsmentioning

confidence: 99%

Huntington’s disease iPSC models—using human patient cells to understand the pathology caused by expanded CAG repeats

Kaye¹,

Reisine²,

Finkbeiner³

2022

Fac Rev

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A major advance in the study of Huntington’s disease (HD) has been the development of human disease models employing induced pluripotent stem cells (iPSCs) derived from patients with HD. Because iPSCs provide an unlimited source of cells and can be obtained from large numbers of HD patients, they are a uniquely valuable tool for investigating disease mechanisms and for discovering potential disease-modifying therapeutics. Here, we summarize some of the important findings in HD pathophysiology that have emerged from studies of patient-derived iPSC lines. Because they retain the genome and actual disease mutations of the patient, they provide a cell source to investigate genetic contributions to the disease. iPSCs provide advantages over other disease models. While iPSC-based technology erases some epigenetic marks, newly developed transdifferentiation methods now let us investigate epigenetic factors that control expression of mutant huntingtin (mHTT). Human HD iPSC lines allow us to investigate how endogenous levels of mHTT affect cell health, in contrast to other models that often rely on overexpressing the protein. iPSCs can be differentiated into neurons and other disease-related cells such as astrocytes from different brain regions to study brain regional differences in the disease process, as well as the cell-cell dependencies involved in HD-associated neurodegeneration. They also serve as a tissue source to investigate factors that impact CAG repeat instability, which is involved in regional differences in neurodegeneration in the HD brain. Human iPSC models can serve as a powerful model system to identify genetic modifiers that may impact disease onset, progression, and symptomatology, providing novel molecular targets for drug discovery.

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Differentiation of hPSCs to Study PRC2 Role in Cell-Fate Specification and Neurodevelopment

Brocchetti

Conforti

2023

Methods in Molecular Biology

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RUES2 hESCs exhibit MGE-biased neuronal differentiation and muHTT-dependent defective specification hinting at SP1

Cited by 5 publications

References 83 publications

In vitro-derived medium spiny neurons recapitulate human striatal development and complexity at single-cell resolution

In vitro-derived medium spiny neurons recapitulate human striatal development and complexity at single-cell resolution

Huntington’s disease iPSC models—using human patient cells to understand the pathology caused by expanded CAG repeats

Differentiation of hPSCs to Study PRC2 Role in Cell-Fate Specification and Neurodevelopment

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