Nature - USA (2020-09-24)

Article

.

c

0.0

0.4

0.8

1.2

Relative

mRNA

level

PEX3 AGPS

si-NC

si-PEX3

si-AGPS

Cardiomyocytes

(CM)

Cardiac progenitor

s

(CP)

Nucleus Cardiac Troponin TNKX2.5Merge

d

ab

55

55

55

70

70

43

70

95

130

55

70

43

43

34

26

Tyrosine

Hydroxylase

NeuN

MAP2

kDa

β-Actin

β-III-tubulin

ParDay 12

SH-SY5Y

*

*

e

Cardiomyocytes (CM): ML210 150nM

30 μM

-2 -1 0

Log 10 (μM RSL3)

iPSC

CM

-2 -1 01

0.0

0.5

1.0

1.5

Log 10 (μM ML210)

Relativ

ev

iabilit

y

j

g h

-2 02468

0.0

0.5

1.0

1.5

Log 2 (day6 / day0)

-Log

adj. p 10

SH-SY6Y (Free fatty acid lipidomics)

-6 -4 -2 0246

0

1

2

3

Log 2 (day12 / day0)

formylmethionine

17-methylstearate

-4 -2 0246

0

1

2

3

4

5

Log 2 (CM / CP)

-Log

adj. p 10

CM/CP free fattyacidlipidomics

C22:6n3

taurochenodeoxycholate

C22:5n6

C20:5n3taurocholate

taurodeoxycholate

C18:2n6

C20:2n 6

C20:3n 6

-2 -1 01

0.0

0.5

1.0

1.5

Log 10 (μM RSL3)

Day0

Day6

SH-SY5Y

Relative

viabilit

y

00 .25

0

25

50

75

100

125

%V

iabilit

y

Cardiomyocytes (CM)

DMSO

z-VAD

Nec-1

Fer- 1

Lip- 1

ML210 (M)

i

RA in

SH-SY5Y 10% FBS

cells 3 Day

RA in

0% FBS

3 Day

BDNF

0% FBS

6 Day

Mature

neurons

Day 0Day 6Day 12100 μm

100 μm

DMSO ML210

Day 12 differentiated SH-SY5Y

oxidized

BODIPY-C1 1

merge with

reduced

BODIPY-C1 1

-Log

adj. 10

p

f

k

Extended Data Fig. 12 | See next page for caption.