Science - USA (2022-03-04)

Winkleret al.,Science 375 , eabi7377 (2022) 4 March 2022 2 of 12

A

B

Vascular

Neurons/glia

Immune

Endothelial

Pericyte

Smooth muscle

Fibroblast

Fibromyocyte

Macrophage

T cell

B cell

Astrocytes

Microglia

Oligodendrocytes

OPCs

Other

Erythrocytes

Neuron 2

Neuron1

E

Donor

Control 1

Control 2

Control 3

Control 4

Control 5

BC ECFBFbMM PC SMCTC

Neu1

AC MG OLOPC RBC

Neu2

Cell Proportion

(%)

0

50

100

CLDN5PECAM1HIGD1BKCNJ8CNN1MYH11 HBA2

DCNAPOD

IGFBP5KCNT2MRC1LYVE1CD3DPTPRC

AFF3BACH2CDH19SCN7A

KCNMA1

GPC6AQP4GFAP

P2RY12

SPP1PLP1PCDH9CSMD1VCANHBB

EC

RBC

PC

SMCFB

FbMM

TC

Neu1BC

Neu2AC

MG

OPCOL

C

D

250

50

75

% Exp.

Avg. Exp.

2

1

0

Fibroblast

Smooth Muscle

Fibromyocyte

FB1

FB2

FbM1

FbM2

SMC2

SMC3

SMC4

SMC5

SMC1

Pericyte

PC

SMC6

SMC7

Perivascular Cells

Endothelial

Art1

Art2

Art3

Cap

Venule

Venous

Endothelial Cells

-0.4

0

0.4

Cap Art

Art

Art SS

Large Art

Cap

Cap Venous

Large VeinInterferon

Art1

Art2

Art3

Cap

Venule

Vein

Cor.

INTS6 SLC3A2

HSPA1A

JUNBVEGFC

MECOMARL15PECAM1TXNIP

MGP

ACKR1IL1R1TSHZ2ATP10A

TMEM132C

MFSD2ASRARP

RGCC

Art1

Venule

Cap

Art2

Art3

Venous

% Exp.

25

50

75

100

Avg. Exp.

2

1

0

Avg. Exp.

1

0

FG

HI

UMAP

UMAP

UMAP DESMYL9

TAGLNGRID2

GLA

RERGLHSPA6HSPA1AHSPA1BAPOE

NDUFA4L2SLC38A11

RN7SKCARMNC11orf96MT2AMT1XMT1MCCL2RGS16

IL6

HIGD1BKCNJ8ATP1A2IGFBP5KCNT2RARACCL19ALDH1A1APOD

MGPDCN

PTGDS

ALDH1A2

IGF2

SMC1

SMC2

SMC3

SMC4

SMC5

SMC6

SMC7

PC

FbM1

FbM2

FB1

FB2

% Exp.

25

50

75

100

Fig. 1. Cells of the human cerebrovasculature.(A) Isolation and cell sampling
from human cerebral cortex. scRNA, single cell mRNA. (B) UMAP visualization
showing cell states from control adult cerebrovasculature (n= 5 donors). (C) Dot
plot showing expression of cell state markers. EC, endothelial cell; PC, pericyte;
SMC, smooth muscle cell; FB, perivascular fibroblast; FbM, fibromyocyte; Mf,
macrophage; TC, T cell; BC, B cell; Neu, neuron; AC, astrocyte; MG, microglia;
OL, oligodendrocyte; OPC, oligodendrocyte precursor cell; and RBC, erythrocyte.
(D) Bar graph showing cell state proportion by donor. Number of cells sequenced
by donor: control 1, 6033 cells; control 2, 25,730 cells; control 3, 22,816 cells;

control 4, 19,302 cells; and control 5, 654 cells. (E) UMAP visualization of

endothelial cell states. Art, arterial; Cap, capillary. (F) Dot plot showing

expression of endothelial cell state markers. (G) Correlation matrix of gene

expression profiles between mouse and human cerebrovascular endothelial

cell states. Mouse data obtained from a previously published database

( 13 ). Art, arterial; Cap, capillary; SS, shear stress. (H) UMAP visualization of

perivascular cell states. FB, perivascular fibroblast; FbM, fibromyocyte;

PC, pericyte; and SMC, smooth muscle cell. (I) Dot plot showing expression

of perivascular cell state markers.

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