Human iPSC-derived hippocampal spheroids: An innovative tool for stratifying Alzheimer disease patient-specific cellular phenotypes and developing therapies

Pomeshchik, Yuriy; Klementieva, Oxana; Gil, Jeovanis; Martinsson, Isak; Hansen, Marita Grønning; Vries, Tessa de; Sancho-Balsells, Anna; Russ, Kaspar; Savchenko, Ekaterina; Collin, Anna; Vaz, Ana Rita; Bagnoli, Silvia; Nacmias, Benedetta; Rampon, Claire; Sorbi, Sandro; Brites, Dora; Markó-Varga, György; Kokaia, Zaal; Rezeli, Melinda; Gouras, Gunnar K.; Roybon, Laurent

doi:10.1016/j.stemcr.2021.10.003

Cited by 7 publications

(19 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Transcriptomic Analysis Identifies Increased Expression of Genes Encoding Major Histocompatibility Complex (MHC)-Class Proteins and Decreased Expression of Genes Involved in Differentiation and Maturation in Human aSYN p.A53T O4 + OLCs. To investigate whether human oligodendrocytes display cellular alterations in PD, we used control (13,14) and PD-derived iPSC lines harboring the heterozygous aSYN variation p.A53T (15) (SI Appendix, Fig. S1).…”

Section: Resultsmentioning

confidence: 99%

“…The generation of iPSC lines CSC-3G, CSC-3S, CSC-32B, CSC-32K, and CSC-32R was previously published (6,15,32). Lines CSC-28N, CSC-36C, CSC-36D, and CSC-36E were recently described (13,14). A similar approach was used to generate iPSCs from an MSA-C patient (iPSC lines CSC-30B; CSC-30C and CSC-30D) and an MSA-P patient (iPSC lines CSC-34D; CSC-34F and CSC-34M; SI Appendix, Fig.…”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Parkinson’s disease and multiple system atrophy patient iPSC-derived oligodendrocytes exhibit alpha-synuclein–induced changes in maturation and immune reactive properties

Azevedo

Teku

Pomeshchik

et al. 2022

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

View full text Add to dashboard Cite

Significance Our results demonstrate the existence of early cellular pathways and network alterations in oligodendrocytes in the alpha-synucleinopathies Parkinson’s disease and multiple system atrophy. They further reveal the involvement of an immune component triggered by alpha-synuclein protein, as well as a connection between (epi)genetic changes and immune reactivity in multiple system atrophy. The knowledge generated in this study could be used to devise novel therapeutic approaches to treat synucleinopathies.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Parkinson’s disease and multiple system atrophy patient iPSC-derived oligodendrocytes exhibit alpha-synuclein–induced changes in maturation and immune reactive properties

Azevedo

Teku

Pomeshchik

et al. 2022

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

View full text Add to dashboard Cite

show abstract

“…Another report from Pomeshchik et al combined SHH inhibition with WNT activation to specify cells toward a dorsal telencephalic fate. Further culturing of these organoids with brain-derived neurotrophic factor (BDNF) allow expansion of hippocampal neural progenitors leading to cellular and structural signatures similar to hippocampus ( 52 ).…”

Section: Region Specific Brain Organoidsmentioning

confidence: 99%

Region Specific Brain Organoids to Study Neurodevelopmental Disorders

Susaimanickam

Kiral

Park

2022

IJSC

View full text Add to dashboard Cite

Region specific brain organoids are brain organoids derived by patterning protocols using extrinsic signals as opposed to cerebral organoids obtained by self-patterning. The main focus of this review is to discuss various region-specific brain organoids developed so far and their application in modeling neurodevelopmental disease. We first discuss the principles of neural axis formation by series of growth factors, such as SHH, WNT, BMP signalings, that are critical to generate various region-specific brain organoids. Then we discuss various neurodevelopmental disorders modeled so far with these region-specific brain organoids, and findings made on mechanism and treatment options for neurodevelopmental disorders (NDD).

show abstract

“…Furthermore, neurons only from the hippocampal spheroids with APP V717I displayed altered cell body size and neurite length, as well as a reduced number of action potential firings and a significantly more depolarised threshold (Ref. 62). Together, these results suggest that the different fAD mutations in APP compared with PSEN1 trigger AD pathology in the hippocampus by mechanistically distinct pathways.…”

Section: Aβmentioning

confidence: 99%

“…A β accumulation was also studied in a hippocampal spheroid model by Pomeshchik et al ., using AD patient-derived iPSCs harbouring either the APP London (V717I) mutation or the PSEN1 R278K mutation (Ref. 62). They observed elevated A β 42/40 ratios in both AD spheroid models compared with control ones; however, only the hippocampal neurons with APP V717I, and not PSEN1 R278K, exhibited a significantly higher intracellular β -sheet structure, indicative of increased protein aggregation.…”

Section: Modelling Of Ad Pathology Using Human Brain Organoidsmentioning

confidence: 99%

Modelling Alzheimer's disease using human brain organoids: current progress and challenges

Yanakiev

Soper

Berg

et al. 2022

Expert Rev. Mol. Med.

View full text Add to dashboard Cite

Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterised by gradual memory loss and declining cognitive and executive functions. AD is the most common cause of dementia, affecting more than 50 million people worldwide, and is a major health concern in society. Despite decades of research, the cause of AD is not well understood and there is no effective curative treatment so far. Therefore, there is an urgent need to increase understanding of AD pathophysiology in the hope of developing a much-needed cure. Dissecting the cellular and molecular mechanisms of AD pathogenesis has been challenging as the most commonly used model systems such as transgenic animals and two-dimensional neuronal culture do not fully recapitulate the pathological hallmarks of AD. The recent advent of three-dimensional human brain organoids confers unique opportunities to study AD in a humanised model system by encapsulating many aspects of AD pathology. In the present review, we summarise the studies of AD using human brain organoids that recapitulate the major pathological components of AD including amyloid-β and tau aggregation, neuroinflammation, mitochondrial dysfunction, oxidative stress and synaptic and circuitry dysregulation. Additionally, the current challenges and future directions of the brain organoids modelling system are discussed.

show abstract

Human iPSC-derived hippocampal spheroids: An innovative tool for stratifying Alzheimer disease patient-specific cellular phenotypes and developing therapies

Cited by 7 publications

References 0 publications

Parkinson’s disease and multiple system atrophy patient iPSC-derived oligodendrocytes exhibit alpha-synuclein–induced changes in maturation and immune reactive properties

Parkinson’s disease and multiple system atrophy patient iPSC-derived oligodendrocytes exhibit alpha-synuclein–induced changes in maturation and immune reactive properties

Region Specific Brain Organoids to Study Neurodevelopmental Disorders

Modelling Alzheimer's disease using human brain organoids: current progress and challenges

Contact Info

Product

Resources

About