Science - USA (2021-12-10)

Shiet al.,Science 374 , eabj6641 (2021) 10 December 2021 8 of 12

A

F G

B

MGE

M1

M2

M3

M4

M5

M6

M7

C

PV+ basket cells

PV+ chandelier cells

SST+ Martinotti cells

SST+ non-Martinotti cells

SST+ LRP cells

LHX6+ LAMP5+ cells

PV+ basket cells

PV+ chandelier cells

SST+ Martinotti cells

SST+ non-Martinotti cells

SST+ LRP cells

LHX6+ LAMP5+ cells

Unassigned

Integrated

Adult LHX6 interneurons

Embryonic MGE cells

PV+

chandelier

cells

PV+ basket

cells SST+ non-

Martinotti cells

SST+ LRP

cells

SST+ Martinotti

cells

LHX6+

LAMP5+

cells

3

5

2

11

8

9

1

7

MGESST 10

MC1

MC3

MC4

MC6

MC5

nMC1

nMC2

MGE

LRP

SST neurons Adult cortex

MGESST 6

MGESST

MGESST

MGESST

MGESST

MGESST

MGESST

MGESST

MGESST

CNTNAP2

CRABP1

ANGPT2

NR2F2

NR2F1

CXCR4

GRIA2

ISL1

LHX8

ZFHX3

ZIC1

MDK

NKX2-1

LHX6

SOX6

ETV1

NFIA

MAF

GBX2

ERBB4

M1M2M3M4M5M6M7

M1

M2

M3

M4

M5

M6

M7

pMGE

Hippocampal interneurons

Neocortical interneurons

GNG5 CXCR4

ERBB4 CRABP1

D

M3

NR2F1

NR2F2

ZFHX3

Cortical

interneurons

Subpallial

cholinergic

neurons

Subpallial

GABAergic

neurons

CRABP1

NKX2-1

ETV1

NFIA

Striatal and

cortical

interneurons

M1

pMGE

M7

M4

M2 M6

Branch 2 Branch 1

MEF2C

MAF

ARX

ZEB2

LHX8

ISL1

ZIC1

GBX2

E

Branch 1

Branch 2

Pseudotime

0 30

GAD2

LHX8

0

4

0

3

1

4

1.0

3.5

0

3

0

6

MGE-2

MGE-1 MGE-2

MGE-1

?

?

M5

4

nMC3

MGESST

Fig. 5. Transcriptional control of early cell specification in the human
MGE.(A) Neuronal diversity of postmitotic cells in human MGE visualized
via t-SNE. (B) Violin plots of DEGs among MGE clusters. (C) Developmental
trajectory of MGE cells are inferred via monocle analysis (with the exception
of MGE-2 cells) and visualized by UMAP. Pseudotime of MGE cells in branches
1 and 2 is shown (top left). (D) Gene expression along the developmental
trajectories of MGE cells is visualized via UMAP. MGE-2 cells comprise GABAergic
and cholinergic subpallial neurons, according to the expression ofGAD2and
LHX8, respectively. Each dot represents an individual cell and colored according
to the expression level (red, high; gray, low). (E) Schematic of hypothetical

genetic programs underlying the early diversification of human MGE cells.

The developmental trajectory linking pMGE (progentiors of the MGE) to MGE-2

cells is uncertain (dotted line) owing to the lack of related progenitor cells in

our dataset. (F) Integration of postmitotic human MGE cells (M2 and M3) and

LHX6+ adult human cortical interneurons is visualized by UMAP. MGE cells were

annotated according to the classification of adult cortical interneurons on the

basis of transcriptional similarities. (G) Riverplot illustrating the relationship

between MGE cell clusters and adult SST+ interneurons. The size of the bars of

MGE cells is normalized to cell numbers. LRP, long-range projection neurons;

MC, Martinotti cells; nMC, non-Martinotti cells.

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