Science - USA (2021-12-10)

Shiet al.,Science 374 , eabj6641 (2021) 10 December 2021 5 of 12

A

B

D

Branch point 1

MGE LGE/CGE

C

towards MGE

towards LGE/CGE

Branch point 1

NFIX

VIP

SST

PAX6

LHX6

NXPH1

MAF

NKX2-1

SOX6

-2 (^02) Branch point 2
PROX1
NFIX
SCGN
NR2F2
NFIB
EBF1
SIX3
FOXP2
ISL1
POU3F4
ZFHX3
PBX3
MEIS2
LGE CGE
-2 0 2
E
1
2
CGE
MGE
LGE
Progenitors
Hippocampal interneurons
Neocortical interneurons
AP1S2
MGE-derived
neurons
CGE-derived
neurons
LGE-derived
neurons
GW9 GW12-13 GW16-18
CALB2
PCDH9
ZNF503
FOXP1
MEIS2
SCGN
NR2F2
CALB2
NR2F1
PDZRN4
Branch point 2
towards LGE
towards CGE
NFIX
Pseudotime
24
0.30
0.25
0.20
0.15
Expressio
n
26 28
Pseudotime
NKX2-1
Expression^1
2
3
0
20 25 30 35
NKX2-1 SFTA3 LHX6
NFIX NR2F2 CALB2
0
3
0
4
0
3
0
4
0
3
0
3
1
2
Pseudotime
0
40
Fig. 3. Transcriptional programs underlying the developmental divergence
of human ganglionic eminences.(A) The cells of human ganglionic eminences
and developing cortical and hippocampal interneurons are integrated and
visualized by UMAP with inferred trajectories. MGE-2 cells were excluded from
this analysis. Potential differentiation trajectories are schematically depicted with
arrows. The pseudotime of ganglionic eminence cells is visualized by UMAP (top
left). (B) Cell distributions at different gestational stages are shown in dark gray.
(C) Heatmaps illustrating genes linked to cell fate divergence at branch points
1 (left) and 2 (right). (D) The expression ofNKX2-1andNFIXdiverged at branch
point 1 and 2, respectively. (E) The expression profile of genes related to cell fate
divergence at branch points 1 and 2 is visualized by UMAP. Each dot represents an
individual cell colored according to the expression level (red, high; gray, low).
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