2021
DOI: 10.1038/s41514-021-00070-x
|View full text |Cite
|
Sign up to set email alerts
|

Klotho inhibits neuronal senescence in human brain organoids

Abstract: Aging is a major risk factor for many neurodegenerative diseases. Klotho (KL) is a glycosylated transmembrane protein that is expressed in the choroid plexus and neurons of the brain. KL exerts potent anti-aging effects on multiple cell types in the body but its role in human brain cells remains largely unclear. Here we show that human cortical neurons, derived from human pluripotent stem cells in 2D cultures or in cortical organoids, develop the typical hallmarks of senescent cells when maintained in vitro fo… Show more

Help me understand this report

Search citation statements

Order By: Relevance

Paper Sections

Select...
2
1
1
1

Citation Types

1
20
0

Year Published

2021
2021
2024
2024

Publication Types

Select...
7
1
1

Relationship

1
8

Authors

Journals

citations
Cited by 23 publications
(21 citation statements)
references
References 61 publications
1
20
0
Order By: Relevance
“…Another 3D organoid model has been developed by cortical neurons that are differentiated from human iPSC were shown to represent typical features of senescent cells, such as increased SA-β-gal activity, p16/p21 expressions, and inflammatory cytokines ( Shaker et al, 2021 ). This senescent phenotype was also accompanied by the significant downregulation of Klotho, a type I transmembrane protein with anti-aging properties ( Kuro-o., 2011 ; Massó et al, 2015 ; Shaker et al, 2021 ).…”
Section: The Tools Of Cellular Senescence Researchmentioning
confidence: 99%
“…Another 3D organoid model has been developed by cortical neurons that are differentiated from human iPSC were shown to represent typical features of senescent cells, such as increased SA-β-gal activity, p16/p21 expressions, and inflammatory cytokines ( Shaker et al, 2021 ). This senescent phenotype was also accompanied by the significant downregulation of Klotho, a type I transmembrane protein with anti-aging properties ( Kuro-o., 2011 ; Massó et al, 2015 ; Shaker et al, 2021 ).…”
Section: The Tools Of Cellular Senescence Researchmentioning
confidence: 99%
“…Since little is known about the 10 murine NSC hub gene expression in NSC of the early developing human CNS, we next investigated their expression in rNSCs and cNSCs derived from human-induced pluripotent stem cells (hiPSCs). To this end, human WTC iPSCs ( Kreitzer et al, 2013 ) were differentiated into NEct or NMP using our published protocols ( Shaker M. R. et al, 2020 ; Shaker et al, 2021a ) to generate populations of rNSCs and cNSCs, respectively ( Figure 2A, B ). As expected, human rNSCs and cNSCs both expressed the pan-NSC markers SOX1, SOX2, and NESTIN ( Figure 2A, B ), while only NMPs expressed BRA-T, confirming their caudal identity.…”
Section: Resultsmentioning
confidence: 99%
“…To address this knowledge gap, we investigated NELL2 expression in human brain organoids generated from human ESC and iPSCs because brain organoids mimic the cellular make-up of early developing human brain, including NSCs, neurons, oligodendroglia, and astrocytes ( Shou et al, 2020 ). The cortical brain organoids we generated from human NEct cells with our previously developed protocol ( Shaker et al, 2021a ) exhibited the layered architecture of the developing cortex with multiple neurogenic zones ( Figure 3A, B ). Immunostaining of 4-week-old brain organoid sections with PAX6 and CTIP2 antibodies confirmed the successful generation of ventricular zone and cortical plate (cortical layer V), respectively ( Figure 3C ).…”
Section: Resultsmentioning
confidence: 99%
“…Klotho gene (KL) expression, increased 10-fold after treatment with 1 ng Metadichol®. Klotho, a type 1 transmembrane protein, has been shown to inhibit TP53 and regulate cellular senescence by repressing the p53/p21 pathway [32]. Thus, klotho prevents aging in primary human broblasts [33] and is neuroprotective.…”
Section: Pathway Studio Analysis Of Neuronal Tfs and Gene Expressionmentioning
confidence: 99%