TY - JOUR

T1 - Modulation of Notch Signaling at Early Stages of Differentiation of Human Induced Pluripotent Stem Cells to Dopaminergic Neurons

AU - Католикова, Наталия Викторовна

AU - Худяков, Александр Александрович

AU - Шафранская, Дарья Дмитриевна

AU - Пржибельский, Андрей Дмитриевич

AU - Машарский, Алексей Эльвинович

AU - Мор, Микаэль Сергеевич

AU - Головкин, Алексей Сергеевич

AU - Зайцева, Анастасия Константиновна

AU - Неганова, Ирина Эриковна

AU - Ефимова, Евгения Викторовна

AU - Гайнетдинов, Рауль Радикович

AU - Малашичева, Анна Борисовна

PY - 2023/1/11

Y1 - 2023/1/11

N2 - Elaboration of protocols for differentiation of human pluripotent stem cells to dopamine neurons is an important issue for development of cell replacement therapy for Parkinson's disease. A number of protocols have been already developed; however, their efficiency and specificity still can be improved. Investigating the role of signaling cascades, important for neurogenesis, can help to solve this problem and to provide a deeper understanding of their role in neuronal development. Notch signaling plays an essential role in development and maintenance of the central nervous system after birth. In our study, we analyzed the effect of Notch activation and inhibition at the early stages of differentiation of human induced pluripotent stem cells to dopaminergic neurons. We found that, during the first seven days of differentiation, the cells were not sensitive to the Notch inhibition. On the contrary, activation of Notch signaling during the same time period led to significant changes and was associated with an increase in expression of genes, specific for caudal parts of the brain, a decrease of expression of genes, specific for forebrain, as well as a decrease of expression of genes, important for the formation of axons and dendrites and microtubule stabilizing proteins.

AB - Elaboration of protocols for differentiation of human pluripotent stem cells to dopamine neurons is an important issue for development of cell replacement therapy for Parkinson's disease. A number of protocols have been already developed; however, their efficiency and specificity still can be improved. Investigating the role of signaling cascades, important for neurogenesis, can help to solve this problem and to provide a deeper understanding of their role in neuronal development. Notch signaling plays an essential role in development and maintenance of the central nervous system after birth. In our study, we analyzed the effect of Notch activation and inhibition at the early stages of differentiation of human induced pluripotent stem cells to dopaminergic neurons. We found that, during the first seven days of differentiation, the cells were not sensitive to the Notch inhibition. On the contrary, activation of Notch signaling during the same time period led to significant changes and was associated with an increase in expression of genes, specific for caudal parts of the brain, a decrease of expression of genes, specific for forebrain, as well as a decrease of expression of genes, important for the formation of axons and dendrites and microtubule stabilizing proteins.

KW - Cell Differentiation

KW - Dopaminergic Neurons/metabolism

KW - Humans

KW - Induced Pluripotent Stem Cells/metabolism

KW - Pluripotent Stem Cells/metabolism

KW - Receptors, Notch/metabolism

KW - Signal Transduction

KW - differentiation

KW - notch intracellular domain (NICD)

KW - RBPJ

KW - dopamine neurons

KW - induced pluripotent stem cells (IPSC)

KW - DAPT

KW - Parkinson’s disease

UR - https://www.mendeley.com/catalogue/be02b030-9a0e-3563-9af0-7d20509ef707/

U2 - 10.3390/ijms24021429

DO - 10.3390/ijms24021429

M3 - Article

C2 - 36674941

VL - 24

JO - International Journal of Molecular Sciences

JF - International Journal of Molecular Sciences

SN - 1422-0067

IS - 2

M1 - 1429

ER -