MATERIALS AND METHODS
Data collection. This research effort proceeded by mining
existing data and literature available online. mRNA expression
information was drawn from microarray and transcriptome datasets
available on the Allen Brain Atlases portal
(https://portal.brain-map.org). Data were not available for mouse brain
development (http://developingmouse.brain-map.org) , so we
analyzed the prenatal and postnatal expression FKBP5 mRNA only in the
rhesus macaque (Macaca mulatta ) and human (Homo sapiens )
brain. Regions of interest (ROIs) including prefrontal cortex, amygdala,
hippocampus, and striatum were selected on the basis of their
involvement in MDD and ELS (Criado-Marrero et al, 2020; Troubat et al.,
2021; Grogans et al., 2022; Pizzagalli and Roberts, 2022). The primary
visual cortex was included as an independent region in the figure as an
example of a non-ROI, to highlight the differences between gene
expression for an individual region which is not relevant to MDD, and
those which are. Adult mouse FKBP5 mRNA expression data were also
retrieved from the Allen Brain Atlases portal
(http://mouse.brain-map.org/gene/show/14006; experiment 70525820, probe
name RP_050317_04_G06). For the re-analyses of FKBP5 mRNA expression
in human and mouse MDD, data were retrieved from the original
publications. Human MDD RNA sequencing (RNAseq) data (Matosin et al.,
2023) consisted of PFC (area BA9) samples from 179 control subjects and
144 MDD cases, previously described in Tao et al. (2017). RNAseq data
from a mouse model of MDD were retrieved from
https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE109315. In this
study, the authors performed RNAseq on prefrontal cortex and hippocampus
from adult C57BL/6N control mice and C57BL/6N mice subjected to chronic
social defeat stress (CSDS); data were normalized using voom and
adjusted for sequencing (vHPC) and library preparation batches (vHPC,
mPFC) with ComBat (Laine et al., 2018).
Data analysis. The human developmental transcriptome and
non-human primate (NHP) microarray microdissection data for the FKBP5
gene were analyzed with Matlab (Mathworks) using the toolbox cbrewer2
version 1.0.0.1 (Lowe, 2023) to generate heat maps. The log2 reads per
kilobase per million (RPKM) values of transcriptome data and z-score
normalized values of microarray data (probe MmugDNA.10638.1.S1_at) were
averaged for donors of the same age, and also across substructures to
achieve the macrostructures (for example, the V1 macrostructure is
composed of substructures including layer I, layer II, etc.).
Supplementary Table 1 reports a full list of the components included in
each macrostructure. In the case of the human data, any time point which
lacked results for more than three macrostructures was excluded.
Supplementary Table 2 summarizes the number of subjects per time point
for the human data, while Supplementary Table 3 reports the same
information for the corresponding non-human primate data points. FKBP5
mRNA expression data from the MDD mouse model (Laine et al. 2018; GEO
accession number GSE109315) were analyzed with Matlab (Mathworks). FKBP5
mRNA expression data from RNAseq human datasets were re-plotted from
Figure 1a of the original paper (Matosin et al., 2023) and analyzed
using Prism 8.0 (GraphPad).
Code Accessibility. The code described in this paper is freely
available online on Zenodo
(https://doi.org/10.5281/zenodo.7525970 ) and GitHub
(https://github.com/BozziNDRLab/Strelevitz_et_al_2023.git ).
The specific toolbox we used in the code was obtained from Lowe (2023).