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Molecular profiling of serotonergic neurons from nonhuman primate embryonic stem cell R366.1
Author(s) -
Reddy Arubala P,
Bunquin Lloyd S,
Sawant Neha,
Reddy Hemachandra
Publication year - 2020
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1002/alz.047367
Subject(s) - biology , embryonic stem cell , neurogenesis , stem cell , embryoid body , microbiology and biotechnology , neuroscience , cellular differentiation , neural stem cell , adult stem cell , genetics , gene
Background In the past decade, knowledge of Alzheimer’s disease advanced exponentially. Many in vitro and in vivo models emerged to conduct the mechanistic target‐oriented study. Midbrain pathogenesis is comparatively newer and unexplored in NDDs Research. We have developed a rhesus embryonic stem cell differentiated from NHP cells . Learning the neurodegenerative study in humans is impossible in human, hence cell model are essential to understand. Objective : This study is to investigate the blueprint of Rhesus stem cell Rh 366.4 in the differentiation of5HT of midbrain Isodendritc core. Newborn neurons are expressing 5HT character further analyzed using TAC and IPA analysis software, and all serotonin‐related mRNA using Human low‐density array. Method Rhesus monkey embryonic stem cells R366.4 (XY) differentiated to serotonin enriched neurons. RNA extracted from ESC colony, Embryoid body, stage N1, proliferation stage N2, and differentiated 5HT neurons. RNA isolated from the previously conducted study hybridized to Affymetrix chip Clariom D Human chip as it has entire RNA species expressing more than 135000 probe set. The more comprehensive and dynamic range of the newer chip. Data analyzed using TAC 4.0 and Ingenuity Pathway Analysis (IPA). In the previous study shows the 366.4 GATA3 driven, FGFR2 dominate, and Sonic hedgehog (Shh) and FEV1 enriched neural cells have many characteristics of serotonin neurons of the dorsoventral axial plate. Result N3 cells 5HT neurons compare to ESC R366.1: Canonical pathway altered are: axonal guidance, integrin signaling, synaptogenesis signaling. network: Cellular movement development, growth, cell proliferation, and survival. Top5 network: cell death and survival, nervous system development. Results: ESC366.4 cells compare to N3 cells (5HT Neurons): Canonical pathways altered are Oxidative phosphorylation, EIF2 signaling, mitochondrial dysfunction, protein ubiquitination. Upstream regulator: function: RNA/DNA damage repair, cell death, and survival, post‐translational modification, nervous system development. Top5 network function: related to disease mechanism of metabolism, development disorder, metabolic disease Analysis active Detail bioinformatic analysis will be presented in the poster. Conclusion R366.1 cell differentiated in early serotonergic neurons, and many pathways and miRNA will be reported 1 st time. The ESC R366.1 is a potential cell line close to human homology essential to study in neural grafting, molecular targets, and cellular metabolism.