title: Trace elements during primordial plexiform network formation in human cerebral organoids.
abstract: Systematic studies of micronutrients during brain formation are hindered by restrictions to animal models and adult post-mortem tissues. Recently, advances in stem cell biology have enabled recapitulation of the early stages of human telencephalon developmentin vitro. In the present work, we analyzed cerebral organoids derived from human pluripotent stem cells by synchrotron radiation X-ray fluorescence in order to measure biologically valuable micronutrients incorporated and distributed into the exogenously developing brain. Our findings indicate that elemental inclusion in organoids is consistent with human brain tissue and involves P, S, K, Ca, Fe and Zn. Occurrence of different concentration gradients also suggests active regulation of elemental transmembrane transport. Finally, the analysis of pairs of elements shows interesting elemental interaction patterns that change from 30 to 45 days of development, suggesting short- or long-term associations, such as storage in similar compartments or relevance for time-dependent biological processes. These findings shed light on which trace elements are important during human brain development and will support studies aimed to unravel the consequences of disrupted metal homeostasis for neurodevelopmental diseases, including those manifested in adulthood.
authors.affiliation: D'Or Institute for Research and Education (IDOR), Rio de Janeiro, Brazil; Institute of Biomedical Sciences, Federal University of Rio de Janeiro, Brazil.
authors.forename: Rafaela C
authors.initials: RC
authors.lastname: Sartore
authors.affiliation: Physics Institute, Federal University of Rio de Janeiro , Brazil.
authors.forename: Simone C
authors.initials: SC
authors.lastname: Cardoso
authors.affiliation: D'Or Institute for Research and Education (IDOR), Rio de Janeiro, Brazil; Institute of Biomedical Sciences, Federal University of Rio de Janeiro, Brazil.
authors.forename: Yury V M
authors.initials: YV
authors.lastname: Lages
authors.affiliation: D'Or Institute for Research and Education (IDOR), Rio de Janeiro, Brazil; Institute of Biomedical Sciences, Federal University of Rio de Janeiro, Brazil.
authors.forename: Julia M
authors.initials: JM
authors.lastname: Paraguassu
authors.affiliation: Federal Institute of Education, Science and Technology of Rio de Janeiro , Brazil.
authors.forename: Mariana P
authors.initials: MP
authors.lastname: Stelling
authors.affiliation: D'Or Institute for Research and Education (IDOR) , Rio de Janeiro , Brazil.
authors.forename: Rodrigo F
authors.initials: RF
authors.lastname: Madeiro da Costa
authors.affiliation: D'Or Institute for Research and Education (IDOR), Rio de Janeiro, Brazil; Institute of Biomedical Sciences, Federal University of Rio de Janeiro, Brazil.
authors.forename: Marilia Z
authors.initials: MZ
authors.lastname: Guimaraes
authors.affiliation: Brazilian Synchrotron Light Laboratory , São Paulo , Brazil.
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Pérez
authors.affiliation: D'Or Institute for Research and Education (IDOR), Rio de Janeiro, Brazil; Institute of Biomedical Sciences, Federal University of Rio de Janeiro, Brazil.
authors.forename: Stevens K
authors.initials: SK
authors.lastname: Rehen
keywords: Cerebral organoids; Development; Human pluripotent stem cells; Neurogenesis; SR-XRF; Trace elements