Ancient DNA, bioengineering and brain "organoids": study of thyroid hormone homeostasis and Alzheimer's Disease markers in NOVA1 gene CRISPR edited stem cells

• Grant number: 18/22763-0
• Support type: Scholarships abroad - Research Internship - Post-doctor
• Effective date (Start): May 01, 2019
• Effective date (End): April 30, 2020
• Field of knowledge: Health Sciences - Medicine
• Principal researcher: Rui Monteiro de Barros Maciel
• Grantee: Janaína Sena de Souza
• Supervisor abroad: Alysson Renato Muotri
• Home Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
• Research place: University of California, San Diego (UC San Diego), United States
• Associated to the scholarship: 17/07053-3 - Effect of thyroid hormone on the brain of 3xTg-AD mice, model of Alzheimer's Disease, on glucose and cholesterol metabolism, BP.PD

Abstract

The understanding about the Neanderthal brain was only possible through study of fossils and found bones. This limitation is being overcome due to the marriage of three fields of science: ancient DNA, genome editing (CRISPR) and organoids, which give us the possibility to explore and understand biomolecular mechanisms. The differentiation of stem cells, with gene editing, into "mini brains", that is, organoids that mimic the cortex opens the door for us to explore and understand the functioning of these cells. Even organoids presenting an early stage of development, we can try to answer important questions such as whether there is any difference in the expression of genes related to homeostasis of the thyroid hormone, very important for neuronal development and, if these cells, cells that mimic Neanderthals cells, have the ability to express proteins related to Alzheimer's disease. The aim of this study is to evaluate thyroid hormone homeostasis and Alzheimer's disease markers in edited cells. To do this, we will differentiate hiPSC and ediPSC into organoids and treat and analyze the expression of TH related genes and AD markers through qPCR, immunohistochemistry, ELISA. We believe that this study will contribute with the understanding of the relevance of TH to brain complex development and AD prevalence. (AU)

Scientific publications

(4)

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

SIMONETTI, LUCIANE; FERREIRA, LUCAS G. A.; VIDI, ANGELA CRISTINA; DE SOUZA, JANAINA SENA; KUNII, ILDA S.; MELARAGNO, MARIA ISABEL; DE MELLO, CLAUDIA BERLIM; CARVALHEIRA, GIANNA; DIAS DA SILVA, MAGNUS R. Intelligence Quotient Variability in Klinefelter Syndrome Is Associated With GTPBP6 Expression Under Regulation of X-Chromosome Inactivation Pattern. FRONTIERS IN GENETICS, v. 12, SEP 20 2021. Web of Science Citations: 0.

GIANNOCCO, GISELE; LETRO KIZYS, MARINA MALTA; MACIEL, RUI MONTEIRO; DE SOUZA, JANAINA SENA. Thyroid hormone, gene expression, and Central Nervous System: Where we are. SEMINARS IN CELL & DEVELOPMENTAL BIOLOGY, v. 114, n. SI, p. 47-56, JUN 2021. Web of Science Citations: 1.

COSTA REIS, LUA TAINA; SENA DE SOUZA, JANAINA; HIROCHI HERAI, ROBERTO; CUNHA, EDUARDO BRUNETTI; RIBEIRO PEREIRA SOARES, JANAINA; SANTOS EL-BACHA, RAMON; DIOGENES AMARAL DA SILVA, VICTOR; AURELIO ROMANO, MARCO; MARINO ROMANO, RENATA; IZABEL CHIAMOLERA, MARIA; GIANNOCCO, GISELE; LIMA COSTA, SILVIA; DIAS DA SILVA, MAGNUS REGIOS; TELLES DA CUNHA LIMA, SUZANA. ntergenerational thyroid hormone homeostasis imbalance in cerebellum of rats perinatally exposed to glyphosate-based herbicid. ENVIRONMENTAL TOXICOLOGY, v. 36, n. 6 JAN 2021. Web of Science Citations: 1.

LAUREANO-MELO, ROBERTO; DOS-SANTOS, RAONI CONCEICAO; DA CONCEICAO, RODRIGO RODRIGUES; DE SOUZA, JANAINA SENA; LAU, RAPHAEL DA SILVA; SOUZA SILVA, SAMANTHA DA SILVA; MARINHO, BRUNO GUIMARAES; GIANNOCCO, GISELE; AHMED, R. G.; CORTES, WELLINGTON DA SILVA. Perinatal fluoxetine treatment promotes long-term behavioral changes in adult mice. METABOLIC BRAIN DISEASE, v. 35, n. 8 AUG 2020. Web of Science Citations: 0.