Science 6.03.2020

(Nancy Kaufman) #1

Sjöstedtet al.,Science 367 , eaay5947 (2020) 6 March 2020 10 of 16


ENPP6

Oligodendrocyte

SLC13A5

Astrocyte

ALDH1L1

ALOX5

Microglia

PYCARD SNTA1

ITGB2

Neuron

KCNAB2

KCNB1

PDE1B

PPP1R14A

MAG

A

C

D

Low tissuespecifici

ty

LymphoidtissuesBlood

Bone marrow

Liver

Muscle tissueAdiposeSkin

RetinaLung

Mouth

tissuesFemale

GI tract
Kidney
Endocrine
glands
Pituit
Pancreasary gland
Male
tissue
s

Bladder

Brain

B

As

tro

cy
te

M

ric
go
ial

Oligode
ndro
Neuron cyte

Brain

Gastrointestinal tract

Kidney

Endocrine glands

Pituitary gland

Pancreas

Bladder

Male tissues

Female tissues

Mouth

Lung

Retina

Skin

Adipose

Muscle tissues

Liver

Bone marrow

Blood

Lymphoid tissues

Normalized expression (NX)

Astrocyte

Microglia

Neuron
Oligodendrocyte

ACACB

C1QB PLTP

CCDC3GREM2FBLN1

CD37 FCGR3B
CD14

FXYD5
HCST
ITGB2

SLC17A7
ATP1A3

APOE

APOENOV
CD109

CCDC80 FBLN1 EBI3

CDH1
FOLH1
MYO5B
CALB1
ALDH4A1 APOE

CD14 SDS APOE

C1QB
C1QA

HLA−DMA

C1QC C1QB
C1QA

CD38

FBLN1
CCDC80

CLCA4
PYGM
KIAA1324

PYGM
S100A1
MYBPC1

CDH1
PLTP

KIAA1324

RIMBP2TUSC3
KIAA1324

PLA2G5 RLBP1RGR

FGFR3
RAPGEFL1

HES1

200 400 600 800

0

1

2

Microglia Astrocyte Neuron Oligodendrocyte

Regional coefficient of variation (CV)

RLBP1

FBLN1

MFNG ALOX5

SUCNR1 RGS20 NWD1 LGR5 ENPP6

SLC5A11

HOXD1
FREM2 YSF

P2RY1 PDE1B NDST3 IP6K3

ST8SIA5 GAD2

TBR1 TRHDE
GRIN2C PLCB4GRM1

RNF43 HTR2C
ANO3 RELN

DRD1

ZIC5

PCSK1
D

Kidney

Smooth muscle

Skeletal muscle

Liver

Spleen Liver

Spleen

Spleen

Fig. 7. The gene expression landscape of 420 putative brain cell type signature
genes in cerebral cortex.(A) The expression variation for the 420 signature
genes in the different brain regions was analyzed on the basis of the coefficient
of variation (CV) of NX values across the 10 regions (see figs. S33 and S34
for expression heatmap and scatterplot across the 10 regions). (B)Theexpression
levels for the individual signature genesin the different tissue types. The most
abundant genes are indicated by gene names (see fig. S32 for expression
heatmap of the signature genes across all tissues). (C) Chord diagram shows
the tissue specificity of brain cell type signature genes. Each link represents the
number of cell type signature genes that are elevated at a tissue level in the


analyzed organ and tissue types. (D) Examples of signature genes and their
protein localization in the different cell types. Microglia signature genes
(ALOX5, ITGB2, and PYCARD) are highly expressed in spleen. Several astrocyte
signature genes, including SLC13A5 and ALDH1L1, have elevated expression in
liver, whereas SNTA1 is highly expressed in skeletal muscle. Neuronal examples
(KCNAB2, KCNB1, and PDE1B) are located in neuronal cell bodies in the brain,
while oligodendrocyte proteins, including MAG, are detected in white matter of
the brain as well as in smooth muscle (PPP1R14A) and renal tubule of kidney
(ENPP6). More detailed expression profiles for all cell signature genes are shown
in figs. S33 to S35. Scale bars, 25mm.

RESEARCH | RESEARCH ARTICLE

Free download pdf