Combined methods to evaluate human cells in muscle xenografts

Bensalah, Mona; Klein, Pierre; Riederer, Ingo; Chaouch, Soraya; Muraine, Laura; Savino, Wilson; Butler‐Browne, Gillian; Trollet, Capucine; Mouly, Vincent; Bigot, Anne; Négroni, Elisa

doi:10.1371/journal.pone.0211522

Cited by 4 publications

(3 citation statements)

References 19 publications

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“…It is possible to quantify accurately up to 0.1 ng of human DNA in a mixture with 100 ng mouse genomic DNA using quantitative PCR (qPCR) ( 9 ) ( fig. S6D ).…”

mentioning

confidence: 99%

MEG3 activates necroptosis in human neuron xenografts modeling Alzheimer’s disease

Balusu,

Horré,

Thrupp

et al. 2023

Science

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Neuronal cell loss is a defining feature of Alzheimer’s disease (AD), but the underlying mechanisms remain unclear. We xenografted human or mouse neurons into the brain of a mouse model of AD. Only human neurons displayed tangles, Gallyas silver staining, granulovacuolar neurodegeneration (GVD), phosphorylated tau blood biomarkers, and considerable neuronal cell loss. The long noncoding RNA MEG3 was strongly up-regulated in human neurons . This neuron-specific long noncoding RNA is also up-regulated in AD patients. MEG3 expression alone was sufficient to induce necroptosis in human neurons in vitro. Down-regulation of MEG3 and inhibition of necroptosis using pharmacological or genetic manipulation of receptor-interacting protein kinase 1 (RIPK1), RIPK3, or mixed lineage kinase domain-like protein (MLKL) rescued neuronal cell loss in xenografted human neurons. This model suggests potential therapeutic approaches for AD and reveals a human-specific vulnerability to AD.

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“…It is possible to quantify accurately up to 0.1 ng of human DNA in a mixture with 100 ng mouse genomic DNA using quantitative PCR (qPCR) ( 9 ) ( fig. S6D ).…”

mentioning

confidence: 99%

MEG3 activates necroptosis in human neuron xenografts modeling Alzheimer’s disease

Balusu,

Horré,

Thrupp

et al. 2023

Science

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“…For xenografted samples, reads were aligned to a joint human plus mouse reference genome (GRCh38 and mm10, build 102) using STAR v2.7.3 7 , and then counted using Subread’s featureCounts v2.0.1 8 , in both cases using default parameters. Read count matrices for human and mouse were treated separately for downstream analysis.…”

Section: Methodsmentioning

confidence: 99%

“…It is possible to quantify accurately up to 0.1 ng of human DNA in a mixture with 100 ng mouse genomic DNA using qPCR 8 (Extended Data Fig. 6d).…”

Section: Main Textmentioning

confidence: 99%

Long noncoding RNA MEG3 activates neuronal necroptosis in Alzheimer’s disease

Balusu

Horré

Thrupp

et al. 2022

Preprint

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Neuronal cell loss is a defining feature of Alzheimer's disease (AD), but it remains unclear how neurons die and how this relates to other defining characteristics of the disease. Existing in vivo AD models only partially recapitulate the neuropathology of AD with very mild or no neuronal cell loss. Here we demonstrate that human neurons xenografted in mouse brain exposed to amyloid pathology develop sarkosyl-insoluble tau filaments, positive Gallyas silver staining, release phosphorylated tau (P-tau181) into the blood, and display considerable neuronal cell loss, providing a model for the induction of full Tau pathology by simple exposure to amyloid pathology in AD. The alterations are specific to human neurons and contrast with the mild effects exhibited in mouse neurons. A core transcriptional program in the human neurons is characterized by strong upregulation of MEG3, a neuron-specific long noncoding RNA. MEG3 is also strongly upregulated in neurons from AD patients in situ. MEG3 expression alone is sufficient to induce necroptosis in human neurons in vitro. Orally administered small molecule receptor-interacting protein (RIP) kinase -1 and -3 inhibitors rescued the neuronal cell loss in this novel AD model. Thus, xenografted human neurons are uniquely sensitive to amyloid pathology, recapitulate all the defining neuropathological features of AD, and ultimately die by necroptosis.

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Abstracts of the 2023 Padua Days of Muscle and Mobility Medicine (2023Pdm3) to be held March 29 - April 1 at the Galileian Academy of Padua and at the Petrarca Hotel, Thermae of Euganean Hills, Padua, Italy

et al. 2023

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At the end of the 2022 Padua Days of Muscle and Mobility Medicine (Pdm3) the next year's meeting was scheduled from 29 March to 1 April 2023. Despite the worsening evolution of the crisis in Eastern Europe, the program was confirmed in autumn 2022 with Scientific Sessions that will take place over three full days in the Aula Guariento of the Galileian Academy of Arts, Letters and Sciences of Padua (March 29, 2023) and then at the Conference Room of the Hotel Petrarca, Thermae of Euganean Hills (Padua), Italy. Collected during autumn and early winter, many titles and abstracts where submitted (about 100 Oral presentations are listed in the preliminary Program by January 31, 2023) confirming attractiveness of the 2023 Pdm3. The four days will include oral presentations of scientists and clinicians from Austria, Bulgaria, Canada, Denmark, France, Georgia, Germany, Iceland, Ireland, Italy, Mongolia, Norway, Russia, Slovakia, Slovenia, Spain, Switzerland, The Netherlands and USA. Together with the preliminary Program at January 31, 2023, the Collection of Abstracts is e-published in this Issue 33 (1) 2023 of the European Journal of Translational Myology (EJTM). You are invited to join, submitting your Last Minute Abstracts to ugo.carraro@unipd.it by March 15, 2023. Furthermore, with the more generous deadline of May 20, 2023, submit please “Communications” to the European Journal of Translational Myology (SCOPUS Cite Score Tracker 2023: 3.2 by January 5, 2023) and/or to the 2023 Special Issue: “Pdm3” of the Journal Diagnostics, MDPI, Basel (I.F. near to 4.0) with deadline September 30, 2023. Both journals will provide discounts to the first accepted typescripts. See you soon at the Hotel Petrarca of Montegrotto Terme, Padua, Italy. For a promo of the 2023 Pdm3 link to: https://www.youtube.com/watch?v=zC02D4uPWRg

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Combined methods to evaluate human cells in muscle xenografts

Cited by 4 publications

References 19 publications

MEG3 activates necroptosis in human neuron xenografts modeling Alzheimer’s disease

MEG3 activates necroptosis in human neuron xenografts modeling Alzheimer’s disease

Long noncoding RNA MEG3 activates neuronal necroptosis in Alzheimer’s disease

Abstracts of the 2023 Padua Days of Muscle and Mobility Medicine (2023Pdm3) to be held March 29 - April 1 at the Galileian Academy of Padua and at the Petrarca Hotel, Thermae of Euganean Hills, Padua, Italy

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