scholarly journals Prenatal Stress Selectively Impairs Neuroligin 1-Dependent Neurogenesis by Suppressing Astrocytic FGF2-Neuronal FGFR1 Axis

2022 ◽  
Author(s):  
Gee Euhn Choi ◽  
Chang Woo Chae ◽  
Mo Ran Park ◽  
Jee Hyeon Yoon ◽  
Young Hyun Jung ◽  
...  
Keyword(s):  
Stem Cell ◽  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Prenatal Stress ◽  
Synapse Formation ◽  
Growth Factor Receptor ◽  
Induced Pluripotent Stem Cell ◽  
Antibody Array ◽  
Fibroblast Growth ◽  
Induced Pluripotent

Abstract Exposure to maternal stress irreversibly impairs neurogenesis of offspring through inducing life-long effects on interaction between neurons and glia under raging differentiation process, culminating in cognitive and neuropsychiatric abnormalities in adulthood. We identified how prenatal exposure to the stress-hormone glucocorticoid impairs synapse formation and subsequent neurogenesis using human induced pluripotent stem cell (iPSC)-derived neural stem cell (NSC) and ICR mice. Following prenatal glucocorticoid exposure, NSC-derived astrocytes were found to be A1-like neurotoxic astrocytes. Moreover, cortisol-treated astrocyte conditioned media (ACM) then specifically downregulated AMPA receptor-mediated glutamatergic synaptic formation and transmission in differentiating neurons, by inhibiting localization of ionotropic glutamate receptor (GluR) 1/2 into synapses. We revealed that downregulated astrocytic fibroblast growth factor 2 (FGF2) and nuclear fibroblast growth factor receptor 1 (FGFR1) of neurons are key pathogenic factors for reducing glutamatergic synapse formation, according to data from RNA sequencing and antibody array. We further confirmed that cortisol-treated ACM specifically decreased the binding of neuronal FGFR1 to the synaptogenic NLGN1 promoter, but this was reversed by FGFR1 restoration. Upregulation of neuroligin 1, which is important in scaffolding GluR1/2 into the postsynaptic compartment, eventually normalized glutamatergic synaptogenesis and subsequent neurogenesis. Moreover, FGF2 pretreatment of a prenatal corticosterone-exposed mouse elevated neuroligin 1 expression and trafficking of GluR1/2 into the postsynaptic compartment, improving spatial memory and depression/anxiety-like behaviors. In conclusion, we demonstrated that neuroligin 1 restoration by astrocytic FGF2 and its downstream neuronal nuclear FGFR1 as a critical target of prenatal stress-induced glutamatergic synaptogenesis and demonstrated its function in controlling both neurogenesis and hippocampal-related behaviors.

scholarly journals POTENSI KOMBINASI INDUCED PLURIPOTENT STEM CELL-DERIVED NEURAL PROGENITOR CELL (IPSC-NPC) DENGAN HIDROGEL CHONDROITIN SULFATE SCAFFOLDS YANG MEMEDIASI BASIC FIBROBLAST GROWTH FACTOR (BFGF) SEBAGAI INOVASI TERAPI TERBARU STROKE ISKEMIK

2020 ◽  
Vol 3 (2) ◽  
Author(s):  
Sisca Sisca ◽  
Nurul Azizah ◽  
M. Salas Al Aldi
Keyword(s):  
Stem Cell ◽  
Growth Factor ◽  
Chondroitin Sulfate ◽  
Fibroblast Growth Factor ◽  
Pluripotent Stem Cell ◽  
Progenitor Cell ◽  
Induced Pluripotent Stem Cell ◽  
Neural Progenitor Cell ◽  
Fibroblast Growth ◽  
Induced Pluripotent

Stroke iskemik adalah jenis stroke yang paling umum terjadi dan merupakan penyakit dengan angka kematian dan kecacatan tertinggi di dunia. Terapi yang ada saat ini dalam menangani stroke masih menyisakan tantangan bagi para peneliti karena belum ditemukannya perawatan yang dapat meregenerasi jaringan otak yang hilang akibat infark. Penggunaan Neural Progenitor Cell (NPC) turunan induced Pluripotent Stem Cell (iPSC) merupakan studi yang berada paling depan dalam tahapan uji praklinis karena diketahui dapat menjadi dan menggantikan neuron serta mempromosikan mekanisme pemulihan endogen seperti angiogenesis. Namun, terdapat hambatan dari penggunaan NPC utamanya pada patofisiologi stroke yang menyebabkan adanya resistensi terhadap terapi seluler. Oleh karena itu, diperlukan kombinasi NPC dengan Scaffold menggunakan Chondroitin sulfate-A (CS-A) berbasis hidrogel yang dapat meningkatkan aliran darah ke inti stroke serta meningkatkan afinitas neurotropik. Kombinasi ini menghasilkan sinergitas terapi yang sangat baik dengan efek utamanya dimediasi oleh basic Fibroblast Growth Factor (bFGF) yang akan memperbaiki kerusakan jaringan di daerah infark. Untuk mengetahui potensi kombinasi NPC dengan Hidrogel CS-A dalam pengobatan stroke iskemik. Literature Review ini disusun menggunakan metode studi pustaka dengan mengumpulkan jurnal yang valid berdasarkan kriteria inklusi dan eksklusi khusus. Kombinasi NPC dengan Hidrogel CS-A secara signifikan meningkatkan perbaikan vaskular, aliran darah kortikal dan hasil perilaku sensorimotor setelah stroke. Peningkatan yang terjadi dimediasi melalui stimulasi pengeluaran bFGF yang mendorong perbaikan jaringan. Efektivitas pemberian NPC secara signifikan dapat ditingkatkan dengan kombinasi Hidrogel CS-A dan telah terbukti dalam berbagai pengujian sehingga diharapkan dapat menjadi upaya terbaru dalam terapi stroke iskemik. 

290 GENERATION OF INDUCED PLURIPOTENT STEM CELLS FROM BOVINE FETAL FIBROBLAST CELLS BY DEFINED FACTORS

2011 ◽  
Vol 23 (1) ◽  
pp. 243 ◽  
Author(s):  
H. G. Cao ◽  
Y. Liu ◽  
H. Q. Yin ◽  
X. P. Sun ◽  
Y. S. Li ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Pluripotent Stem Cells ◽  
Leukemia Inhibitory Factor ◽  
Fibroblast Cells ◽  
Fibroblast Growth ◽  
Fetal Fibroblast ◽  
Induced Pluripotent

Induced pluripotent stem cells (iPS) have broad potential applications in drug screening, regenerative medicine, and basic biology, and using iPS as starting materials that have identical properties to embryonic stem cell would probably revolutionize the production of gene-targeted livestock. However, iPS in livestock is still lacking except for in pigs. Instructed by Yamanaka’s idea, in the current study we attempted to generate bovine iPS from fetal fibroblast cells (bFF; from a fetus 2.5 months old after gestation) by using 4 defined transcriptional factors: Oct-4, Sox2, Klf4, and c-Myc. A lentivirus haboring the 4 factors acted as a vehicle to transfect the bFF. One bFF cell line was infected for at least 3 replicates. After transfection, the treated bFF were then cultured in DMEM supplemented with 4 ng mL–1 of basic fibroblast growth factor and 1000 IU mL–1 of leukemia inhibitory factor at 37.5°C, 5% CO2, on the mouse embryonic feeder cells pretreatd with mitomycin C. From Day 16 after the onset of induction, morphology of a few typical spindle-like bFF gradually changed into round, ball-like cells and grew into colonies. Afterward, when these colonies were harvested and subcultured in stem cell medium supplemented with 1000 IU mL–1 of leukemia inhibitory factor and 4 ng mL–1 of basic fibroblast growth factor, new colonies with clear-cut, round edge emerged, and the cells in the colonies had increased nuclear:cytoplasm ratio, kept normal karyotype up to 10 passages, and were alkaline phosphatase staining positive. We also found that the cells exhibited part of the stem cell markers, as evidenced by being Nanog, SSEA1 positive but SSEA3 and TRA-60 negative. Moreover, embryoid bodies could be formed in vitro, and terotoma formation after injection into nude mice also displayed 3 layers. Taken together, we found that 4 lentivirus-mediated, defined transcriptional factors could successfully induce bFF into iPS-like cells. H. G. Cao and Y. Liu contributed equally to this work. The corresponding authors are Y. H. Zhang and X. R. Zhang. This work was supported by NSFC (30800784/c120103, 30700574), 973 (2009CB941004).

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