Science - USA (2021-12-10)

Shiet al.,Science 374 , eabj6641 (2021) 10 December 2021 4 of 12

RGC

IPC Pseudotime

0

5

GW9 12 13 16 18

pL3

pM4

pM3

pM1

pM2

pL2

pL1

pC1

pC3

pC2

SIX3+ cells (%

)

GW10 GW12 GW16

B C

D

E

F

FABP7

VIM

HES1

ID4

HES5

PTPRZ1

FAM107A

SFRP1

LIX1

NTRK2

GAD2

DLX5

SOX4

DLX2

KPNA2

DCX

ASCL1

SOX11

DLX6

SP9

ARL4D

TMSB10

ARX

RGC IPC

1

SVZ

G

LGE

GW12 SIX3/Ki67/DAPI

1

MGE

2

ic

Str

MGE

LGE

CGE

2

SVZ

0.5 11.5 2

pM4

pMGE pM1 pM2

pM3

pLGE pL1 pL2

pL3

pCGE pC1 pC2

pC3

HES1 FAM107A

ASCL1 OLIG2

DLX2 DCX

pseudo-laminapseudo-differentiation

VZ

SVZ

A

Frequency

0.2 0.4 0.6 0.8

0

0.1

0.2

0.3

0

0.1

0.2

0.3

0.4

0

0.1

0.2

0.3

0.4

0.5

NES HES1 NTRK2

ASCL1 DLX2

VIM

FAM107A HOPX

0

4

0

4

0

3

0

4

0

3

0

3

0

5

0

3

0

3

CALB2

0.5

GSX2

3

NKX2-1

0

3

0

3

NR2F2

0

3

PAX6

0

2

PROX1

SOX6

1

3

0

3

VIP

pC1

pC2

pL2

pL3

pL1

pM1

pM2

pM3

pM4

pC3

LHX6SOX

6

DLX6SFTA3

NKX2-1

RIC3GSX

1

MBIPOLIG2

PCDH17

NR2F2NR2F

1

NTRK

2

DLX5RBP1

VIP

CALB2SCGNZFHX3MEIS2ZNF503

SIX3

PHLDA1

GLI3

LGALS1

PAX6GSX2HEY1

*** ** * ******

avg.exp.scaled ●●

2.5 0.5 2.5

avg. exp. scaled

-2

2

Fig. 2. Cell diversity and genetic regulation of progenitor cells in the
human ganglionic eminences.(A) Clustering of individual progenitor cells in
the human ganglionic eminences (top left) and gene expression visualized by
UMAP. Each dot represents an individual cell colored according to the expression
level (red, high; gray, low). The developmental trajectory of progenitor cells is
analyzed via pseudotime alignment (top right). The inset illustrates the ratio of
RGCs and IPCs among ganglionic eminence progenitor cells from GW9 to GW18.
(B) Heatmap illustrating DEGs that distinguish between RGCs and IPCs in the
human ganglionic eminences. (C) Gene expression patterns along pseudo-
differentiation (xaxis) and pseudo-lamina (yaxis) coordinates. (D) Cell diversity
among progenitor cells in the human ganglionic eminences visualized by

t-distributed stochastic neighbor embedding (t-SNE). The regional identity of

progenitor cells was established according to their characteristic patterns

of gene expression. (E) DEGs among progenitor cells. The relationships among

subclusters of GE progenitors is illustrated via dendrogram. The size of the

dots and the color bar were scaled with the average expression of the

corresponding genes. (F) Expression of SIX3 and Ki67 in the human LGE and

MGE at GW12. The areas in white boxes are shown at high magnification.

Scale bars, 200mm (left), 20mm (right). (G) Quantification of the cell ratio of

SIX3+ cells in LGE, MGE, and CGE cells at GW10, GW12, and GW16, respectively.

Data are presented as means ± SEM (n= 4 samples from three individual

experiments; *P< 0.05, **P< 0.01, ***P< 0.001, one-way analysis of variance).

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