Gene expression atlas of energy balance brain regions


Energy balance is controlled by interconnected brain regions in the hypothalamus, brain stem, cortex and limbic system; the details of the transcript expression “signatures” of these regions can help elucidate the pathophysiology underlying obesity. RNA sequencing was conducted on P56 C57BL/6NTac male mice and E14.5 C57BL/6NTac embryos punch-biopsies in 16 obesity-relevant brain regions. Self-renewing mouse embryonic stem cells (mESCs) were included as a control.

This data portal is designed to serve as a resource for researchers to interrogate their genes of interest across three metrics: transcripts/million reads, differential expression between all brain regions, or differential expression compared to mESCs.


Corresponding Paper

De Rosa MC, Glover H, Stratigopoulos G, LeDuc CA, Su Q, Shen Y, Sleeman MW, Chung WK, Leibel RL, Altarejos J, Doege CA (2021) Gene expression atlas of energy balance brain regions. JCI Insight; 6(16)


Abstract

Energy balance is controlled by interconnected brain regions in the hypothalamus, brain stem, cortex and limbic system. Gene expression signatures of these regions can help elucidate the pathophysiology underlying obesity. RNA sequencing was conducted on P56 C57BL/6NTac male mice and E14.5 C57BL/6NTac embryos punch-biopsies in 16 obesity-relevant brain regions. The expression of 190 known obesity-associated genes (monogenic, rare and low-frequency coding variants, genome-wide association studies (GWAS), syndromic) were analyzed in each anatomical region. Genes associated with these genetic categories of obesity had localized expression patterns across brain regions. Known monogenic obesity causal genes were highly enriched in the arcuate nucleus of the hypothalamus and developing hypothalamus. The obesity-associated genes clustered into distinct ‘modules’ of similar expression profile and these are distinct from expression ‘modules’ formed by similar analysis with genes known to be associated with other disease phenotypes (type 1 and type 2 diabetes, autism, breast cancer) in the same energy balance-relevant brain regions.

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Brain regions

Embryonic Brain (E14.5)
THy/Phy:
Terminal Hypothalamus (Rostral Hypothalamus)/Peduncular (Caudal) Hypothalamus
F: Forebrain
M: Midbrain
H: Hindbrain

Adult Brain (P56)
FRP:
Frontal Pole, Cerebral Cortex
ACA: Anterior Cingulate Area
ACB: Nucleus Accumbens
VTA: Ventral Tegmental Area
LHA: Lateral Hypothalamic Area
PVH: Paraventricular Nucleus
DMH: Dorsomedial Nucleus of the Hypothalamus
VMH: Ventromedial Hypothalamic Nucleus
ARH: Arcuate Hypothalamic Nucleus
PB: Parabrachial Nucleus
NTS: Nucleus of the Solitary Tract
DVC: Dorsal-Vagal Complex
ENT: Entorhinal Area
CENT2: Central Lobule II
CUL4,5: Culmen Lobules IV-V
UVU: Uvula (IX)
CBN: Cerebellar Nuclei
FL: Flocculus

Mouse embryonic stem cells
mESC (B6-1):
Mouse Embryonic Stem Cells, clone 1
mESC (B6-2): Mouse Embryonic Stem Cells, clone 2


Metrics
Transcripts/million

Outputs transcripts per million (TPM) for up to 4 replicates, with mean and standard deviation

DEGs: Differential Gene Expression

Outputs log2 fold change and standard error for each brain region comparared to all other brain regions or each brain region compared to mESCs. Also outputs corresponding p-value, Benjamini-Hochberg adjusted p-value and mean counts


Further details

De Rosa MC, Glover H, Stratigopoulos G, LeDuc CA, Su Q, Shen Y, Sleeman MW, Chung WK, Leibel RL, Altarejos J, Doege CA (2021) Gene expression atlas of energy balance brain regions. JCI Insight; 6(16)


Contact

Please contact hg2553@cumc.columbia.edu with any questions or issues.