Modulation of Notch Signaling at Early Stages of Differentiation of Human Induced Pluripotent Stem Cells to Dopaminergic Neurons

Katolikova, N.; Khudiakov, Aleksandr; Shafranskaya, Daria; Prjibelski, Andrey D.; Masharskiy, Alexey E.; Mor, Mikael S.; Головкин, А. С.; Zaytseva, Anastasia; Neganova, Irina; Efimova, Evgeniya V.; Gainetdinov, Raul R.; Malashicheva, Anna

doi:10.3390/ijms24021429

Cited by 3 publications

(3 citation statements)

References 34 publications

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“…We found only sporadic expression of TAAR5 (Figure 2) in analyzed cell lines at any point of the differentiation process and did not find the expression of any other types of TAARs in our samples. Then, we differentiated three human IPSC lines (AD3, WTSIi004-A, WTSIi032-A) to DA neurons by the protocol described previously [30] and analyzed the TAARs' expression using TaqMan Realtime PCR in various time points of differentiation. We found only sporadic expression of TAAR5 (Figure 2) in analyzed cell lines at any point of the differentiation process and did not find the expression of any other types of TAARs in our samples.…”

Section: Taars Are Expressed At Low Levels In a Number Of Human Ipsc ...mentioning

confidence: 99%

“…We compared the results of the analysis performed on the data from the open sources with data obtained by TaqMan Realtime PCR during the differentiation of human IPSC lines AD3, WTSli004-A and WTSli032-A into DA neurons, made using protocol described previously [30] (Figure 2), where samples for RNA isolation were collected from undifferentiated human IPSCs, on days 12 and 53. Using TaqMan Realtime PCR, we did not find any expression levels of TAAR1, TAAR2, TAAR6, TAAR8 or TAAR9 at any of the stages of differentiation of human IPSCs into dopaminergic neurons.…”

Section: Taars' Profiles Of Expression Are Changed During Differentia...mentioning

confidence: 99%

“…Differentiation of human IPSCs was performed according to the protocol, which was previously described by [30]. Briefly, for differentiation, human IPSCs were harvested with TrypLE Select Enzyme (Gibco, Paisley, UK) and seeded into 6-well plates coated with Geltrex/Knockout DMEM, at a density of 4 × 10 5 cells per well.…”

Section: Differentiation Of Human Ipscsmentioning

confidence: 99%

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Expression Pattern of Trace Amine-Associated Receptors during Differentiation of Human Pluripotent Stem Cells to Dopaminergic Neurons

Katolikova,

Vaganova,

Shafranskaya

et al. 2023

IJMS

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Trace amine-associated receptors (TAARs), which were discovered only in 2001, are known to be involved in the regulation of a spectrum of neuronal processes and may play a role in the pathogenesis of a number of neuropsychiatric diseases, such as schizophrenia and others. We have previously shown that TAARs also have interconnections with the regulation of neurogenesis and, in particular, with the neurogenesis of dopamine neurons, but the exact mechanisms of this are still unknown. In our work we analyzed the expression of TAARs (TAAR1, TAAR2, TAAR5, TAAR6, TAAR8 and TAAR9) in cells from the human substantia nigra and ventral tegmental areas and in human pluripotent stem cells at consecutive stages of their differentiation to dopaminergic neurons, using RNA sequencing data from open databases, and TaqMan PCR data from the differentiation of human induced pluripotent stem cells in vitro. Detectable levels of TAARs expression were found in cells at the pluripotent stages, and the dynamic of their expression had a trend of increasing with the differentiation and maturation of dopamine neurons. The expression of several TAAR types (particularly TAAR5) was also found in human dopaminergic neuron-enriched zones in the midbrain. This is the first evidence of TAARs expression during neuronal differentiation, which can help to approach an understanding of the role of TAARs in neurogenesis.

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Section: Taars Are Expressed At Low Levels In a Number Of Human Ipsc ...mentioning

confidence: 99%

Section: Taars' Profiles Of Expression Are Changed During Differentia...mentioning

confidence: 99%

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Expression Pattern of Trace Amine-Associated Receptors during Differentiation of Human Pluripotent Stem Cells to Dopaminergic Neurons

Katolikova,

Vaganova,

Shafranskaya

et al. 2023

IJMS

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Comprehensive analysis of NOTCH pathway with tumor environment in pancreatic adenocarcinoma

Wang,

Yin,

Chen

et al. 2024

Oncologie

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Objectives Pancreatic adenocarcinoma (PAAD) ranks among the most prevalent malignant neoplasms, and multiple pathways are involved in its pathogenesis, including the NOTCH pathway. However, the variable biological functions of the pathway in PAAD are controversial. Methods RNA-seq data for PAAD was analyzed using data from The Cancer Genome Atlas and Genotype-Tissue Expression databases. Utilizing Kaplan-Meier survival curves and Cox regression analyses, we examined the prognostic significance. The tumor microenvironment and immunotherapy responses were investigated using ssGSEA, ESTIMATE, and TIDE models. Functional enrichment analysis was used to explore gene functions. Results We identified NOTCH2, JAG1, NOTCH4, and DLL3 as high-priority members of the NOTCH pathway that modulates PAAD. Elevated NOTCH2 and JAG1 levels were markedly linked to reduced overall survival (OS), while increased NOTCH4 and DLL3 levels were significantly related to extended OS. Immune analyses showed that NOTCH-based scores were closely related to the immune microenvironment. NOTCH scores were not only closely correlated with tumor-infiltrating immune cells, but also with immunologically activated and immune checkpoint gene expression. The high NOTCH score group had a higher proportion of tumor-infiltrating immune cells and had better responses to immune checkpoint inhibitor therapy. Conclusions These data indicate that NOTCH2, JAG1, NOTCH4, and DLL3 could function as efficient prognostic biomarkers and therapeutic targets in PAAD, and patients with a high NOTCH score may have a significant response to immune checkpoint inhibitor treatment.

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The Neuroanatomy of Induced Pluripotent Stem Cells: In Vitro Models of Subcortical Nuclei in Neurodegenerative Disorders

Galgani,

Scotto,

Giorgi

2024

CIMB

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Neuromodulatory subcortical systems (NSSs) are monoaminergic and cholinergic neuronal groups that are markedly and precociously involved in the pathogenesis of many neurodegenerative disorders (NDDs), including Parkinson’s and Alzheimer’s diseases. In humans, although many tools have been developed to infer information on these nuclei, encompassing neuroimaging and neurophysiological methods, a detailed and specific direct evaluation of their cellular features in vivo has been difficult to obtain until recent years. The development of induced pluripotent stem cell (iPSC) models has allowed research to deeply delve into the cellular and molecular biology of NSS neurons. In fact, iPSCs can be produced easily and non-invasively from patients’ fibroblasts or circulating blood monocytes, by de-differentiating those cells using specific protocols, and then be re-differentiated towards neural phenotypes, which may reproduce the specific features of the correspondent brain neurons (including NSS ones) from the same patient. In this review, we summarized findings obtained in the field of NDDs using iPSCs, with the aim to understand how reliably these might represent in vitro models of NSS. We found that most of the current literature in the field of iPSCs and NSSs in NDDs has focused on midbrain dopaminergic neurons in Parkinson’s disease, providing interesting results on cellular pathophysiology and even leading to the first human autologous transplantation. Differentiation protocols for noradrenergic, cholinergic, and serotoninergic neurons have also been recently defined and published. Thus, it might be expected that in the near future, this approach could extend to other NSSs and other NDDs.

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Modulation of Notch Signaling at Early Stages of Differentiation of Human Induced Pluripotent Stem Cells to Dopaminergic Neurons

Cited by 3 publications

References 34 publications

Expression Pattern of Trace Amine-Associated Receptors during Differentiation of Human Pluripotent Stem Cells to Dopaminergic Neurons

Expression Pattern of Trace Amine-Associated Receptors during Differentiation of Human Pluripotent Stem Cells to Dopaminergic Neurons

Comprehensive analysis of NOTCH pathway with tumor environment in pancreatic adenocarcinoma

The Neuroanatomy of Induced Pluripotent Stem Cells: In Vitro Models of Subcortical Nuclei in Neurodegenerative Disorders

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