Science - USA (2021-12-10)

Shiet al.,Science 374 , eabj6641 (2021) 10 December 2021 6 of 12

D2 MSN

D1 MSN

(TSHZ1)

Striatal

projection neuron

precursors

OB

precursors

D1 MSN

(PDYN)

L1

L2

L3

L4

L5

L6

L7

ABLGE

FH

CHD7

DLX5

ID2

PAX6

MEIS2

TLE4

FOXP1

ZNF503

TSHZ1

FOXP2

PBX3

ERBB4

TAC1

EBF1

ISL1

ZNF503

PENK

CXCL12

SP9

CHD7

C

CNTNAP2

0

3

0

3

0

3

0

3

FOXP2

FOXP1

0

4

0

3

PDYN

TSHZ1 PENK

DRD1

GSX2

ID2

EBF1

ISL1

0

4

0

3

0

4

0

3

0

3

0

2

L1

L2

L3

L4

L5

L6

L7

pLGE

DE

-3 2

Striatal

potential

Enriched

GO terms

log10 (adjusted

p-value)

Olfactory bulb

development

Regulation of

cell migration

-0.5159

-0.4361

Chemical synaptic

transmission

Regulation of

synaptic plasticity -0.1278

Cell division -14.7037

Cell proliferation-3.1211

-0.7408

OB

potential

-2 2

PENK

PHLDA1

ZADH2

SIX3

SP9

CXCL12

ID4

ZFHX4

TSHZ1

LHFP

ERBB4

FOXP2

PBX3

PBX1

TAC1

EBF1

ISL1

ZNF503

CNTNAP2

NTRK3

GAP43

ZNF521

D2 MSN D1 MSN

(TSHZ1)

D1 MSN

(PDYN)

D2 MSN

precursor

D1 MSN

(TSHZ1)

precursor

D1 MSN

(PDYN)

precursor

6

0

• 6
  Log

Fold change 2

PDYN

HCRTR2

PCSK1N

SCG5

NPY

TENM1

GALP

GPR149

SORCS1

PENK

MCHR1

ECEL1

TAC3

TAC1

OPRL1

NPY1R

Striatal

potential

OB

potential

0

0.1

0.2

0.3

0.4

0.5

0.6

EnrichmentScore(ES)

Neuropeptide

signaling pathway

Striatal

potential

OB

potential

OB neuron

precursor

Striatal

potential

OB

potential

G

L3

L4

L5

L6 L7

pLGE

L1

L2

LMO4IGFBP5

CXCL12PEG10

PCSK1N

BCL11ABCL11BENC1EBF1

CNTNAP2

TLE4

FOXP1

APOL4

TMEM123

ANKS1B

ARL4D

SH3BGRL3

RND3

FDR-ajusted P value (-log10)

100

200

300

(^0) Fold change [log2]
-1.0 -0.5 0.0 0.5 1.0 1.5
CHD7DLX5
HMGN2DLX2
PDE4DIP
PAX6
ID2
CALB2
NFIA
CXCR4
MEIS2
NSG2
ZNF503
AC004158.3
VCANSIX3
RBFOX1 ZFHX3
ETFBZFHX4ID4
ISL1
TAC1
NOVA1
Striatal
potential
OB
potential
0
3
CHD7
ISL1
0
3
ZFHX4
0
3
Pseudotime
0
50
I
Fig. 4. Transcriptional regulation of LGE development.(A) Unsupervised
clustering of human LGE postmitotic cells and gene expression patterns
visualized by t-SNE. Each dot represents an individual cell colored according
to the expression level (red, high; gray, low). (B) Developmental trajectory of
LGE cells visualized by UMAP. Pseudotime for individual cells is also shown
(top right). (C) Gene expression profile along the developmental trajectories
of LGE cells visualized via UMAP. (D) Volcano plot of DEGs for LGE cells
with OB and striatal potential. (E) Heatmap illustrating the bifurcation of
gene expression along the developmental trajectory of LGE cells committed to
OB and striatal fates. (FandG) The neuropeptide signaling pathway is
enriched in LGE cells with striatal potential. (H) Heatmap illustrating
DEGs enriched inTSHZ1+D1MSN,PDYN+ D1 MSNs, and D2 MSNs.
(I) Schematic of hypothetical genetic programs underlying the early
diversification of human LGE cells.
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