Nature - USA (2019-07-18)

Article reSeArcH

ET03 ET04 ET05 ET01 ET02

Log

(S phase module) 2

●●●●●●

●● ●●

●●●● ●● ●●

●● ●● ●●

●●

●●●● ●●●●

●●●● ●●●●●●●● ●● ●●

●●

●● ●● ●●

●● ●●●●

●● ●●

●●

●●●●●●●● ●● ●●

●● ●● ●●

●● ●●

●● ●●●● ●●

●●●●●●

●● ●●

●● ●●●● ●●

●● ●●

●● ●●●●●● ●●

●●●●●●●●●● ●●●●

●● ●●●●●●

●●

●● ●●

●●●● ●● ●●

●● ●●

●●

●● ●●

●●●● ●●

●● ●●●●

●● ●●

●● ●● ●●

●● ●● ●● ●●

●● ●● ●● ●● ●●

●●

●● ●● ●●

●● ●●

●● ●● ●●

●●

●●●●●●●● ●●

●●

●● ●●

●●●●

●●

●● ●● ●●

●● ●●

Log 2 (G2M phase module)

P = 0.71

P =1.4 x 10-4

P = 6.3 x 10-4

P = 0.53

P = 0.97

P = 0.040 P = 0.0013

P = 0.98

4

5

6

7

8

9

3

4

5

6

7

8

●●

● ●

●●

●● 5

6

7

4

5

6

7

8

● ● 4

5

6

7

8

●

P = 0.0098

4

5

6

7

3

4

5

6

7

● ●^4

5

6

7

4

5

6

7

4

5

6

7

●

P = 0.0070

P = 0.015 P = 0.017 P = 0.068 P = 2.7 x 10-5

4

5

6

7

● ● ● 4

5

6

7

(^4) ●● ●
5
6
7
●●
3
4
5
6
7
●
●
4
5
6
7
P = 6.4 x 10-5
P = 0.66 P = 0.31 P = 0.029
3
4
5
6
7
2
4
6
●●
●
●●
●
●●●●
4
5
6
7
2
3
4
5
6
7
●●
●
P = 0.22
P = 0.85 P = 0.92 P = 0.80
4
5
6
7
8
2
4
6
8
●●
●
2
4
6
8
●●●
●
●●
3
4
5
6
7
8
P = 0.13
P = 0.27
Log
(Cell cycle module) 2
P = 0.74 P = 0.57
4
5
6
7
8
●
4
5
6
7
8
4
5
6
7
8
4
5
6
7
8
P = 0.75
ET03
WT MUT
●●
●●
●●
●●●●
●●●●
●●●●●●●●
●●
●●
●●●● ●●
●●
●●●●
●●●●●●
●● ●●
●●●●
●●
●●●●●●●●●●●●●●
●●●●●●●●●●●●●●●●
●●●●●●●●●●●●
●●●●●●●●●●●●●●
●●
●●●●●●●●●●●● ●●
●●●●●● ●●
●●●●●●
●● ●●●●
●●●●
●●●●
●●
●●
●●●●
●●
●●
●●
●●●●●●
●●
●●●●●●
●●
●●
●●
●●
●●●●●●●●●●●●●●●●
●●●●
●●
●●●●●●●●●●●●●●●●●●●●●●●●
●●
●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●
●●
●● ●●●●
●●●●●●●●●●●●●●●●●●
●● ●●
●●●●●●●●●●●●●●●●●●●●●●●●●●●●
●●●●●●●●●●●●
●●●● ●●●●
●●
●●●●●● ●●●●
●●●●●●●●●●●●●●
●●●●●●●●●●●●●●●●●●
●●●● ●●
●●
●●●●●●●●
●●●●●●
●●
●●●●
●●
●●●●●●
●●●●
●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●
●●●●●●
●●
●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●
●● ●●
●●●●●●●●●●●●●●●●●●●●
●●●●
●●●●●●●●●●●●
●●
●●●●●●●●●●●●●●●●●●●●●●●●●●●●
●●●●●●●●●●●●●●●●●●●●●●●●●●●●
●●
●● ●●●●
●●●●●●●●●●●●●●●●●●●●●●
●●
●●●●●●●●●●●●●●●●●●●●
●● ●●●●
●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●
●●
●●●●●●●●●●
●●
●●●●●●●●●●●●●●
●●●●●●
●●
●●●●
●●
●●
●●●●
●●
●●●●●●
●●
●●●●
●●●●
●●
●●●●
●●
●●●●●●●●●●●●●●●●
●●
●●
●●
●●●●
●●
●● ●●
●●
●●●●
●●
●●
●● ●●●●
●●
●●
●●
●●●●●●●●●●●●
●●
●●
●●
●●●●●●●●●●●●●●●●●●●●●●●●●●
●●
●●
●●●●●●●●●●
●●
●●
●●
●●●●●●
●●●●●●●●●●
●●
●●
●●●●
●●●●●●
●●
●●
●●
●●●●●●●●
●●
●●
●●●●
●●●●
●●
●●
●●
●●
●●
●●●●
●●●●●●●●
●●●●●●
●●
●● ●●
●●●●
●●●●●●●●●●
●●
●●
●●
●●●●
●●●●●●●●
●●●●●●●●●●●●●●●●●●●●●●
●●●●
●● ●●●●●●
●●
●●●●
●●
●●
●●●●●●
●●
●●
●●●●●●
●● ●● ●●
●●●●●●
●●
●●
●●●●
●●
●●●●●●●●●●●●●●
●●
●● ●●
●●
●●
●● ●●
●●●●
●●
●●●●
●●
●●
●●●●●●●●●●
●●
●●
●●●●●●●●●●
●●
●●●●●●●●●●●●●●●●●●●●●●●●●●●● ●●
●●●●
●●
●●●●●●
●●
●●●●●●●●●●●●
●●
●●
●●
●●
●●●●●●
●●●●
●●
●●●●●●
●●●●●●
●●●●
●●●●●●●●●●●●●●
●●
●●
●●
●●●●
●●
●●
●●
●●
●●●●
●● ●●
●●
●● ●●
●●●●●●
●●
●●
●●●●●●
●●
●●●●●●●●●●●●
●●
●●●●●●●●●● ●●
●●
●●
●●
●●●●●●●●●●
●●
●●
●●●●
●●
●●●●
●● ●●
●●
●●
●●
●●
●●●●
●●
●●●●●●●●●●●●●●
●●
●●●● ●●
●● ●●
●●
●●
●●
●●
●● ●●
●●
●●●●●●●●●●●●
●●
●●
●●●●
●●
●●
●●
●● ●●
●●
●●●●●●
●●
●●
●●
●●
●● ●●
●●
●●●●
●●
●●
●●●●●●
●●
●●
●●
●●●●
●●
●●●●●●●●
●●
●●●●●●●●●●●●●●●●●●
●●
●●
●●
●●●●
●●
●●●●●●●●●●●●●●●●
●●●●●●
●●
●●
●●
●●●●
●●●●●●
●●●●●●
●●●●
●●●●●●●● ●●
●●●●
●●
●●●● ●●
●●●●●●●●
●●
●●
●●●●●●●●●●
●●
●●●●●●
●●
●●
●●
●●●●
●●
●●
●●●●
●●
●●●●●●●●●●●●●●●● ●●●●
●●●●
●●●●●●●●●●●●
●●
●●●●
●●
●●●●●●●●
●●●●●●●●●●●●●●●●
●●●●
●●
●●●●●●
●●●●●●●●
●●
●●
●●
●●●●
●●
●●●●●●●●●●●●●●
●●
●●●●
●●
●● ●●
●●●●●●●●
●● ●●
●●
●●
●● ●●●●●●
●●
●●●●●●●●●●
●●●●●●●●
●●●●●●●●●●●●●●
●●●●
●●●●●●●●●●●●●●●●●●●●●●●●●●●●
●● ●●
●●●●●●●●●●●●
●●
●●
●●
●●●●
●●
●● ●●
●●●●●●
●●●●●●
●●●●●●●●
●●
●●●●●●●●●●
●●●●
●●
●●●●●●●●●●●●●●
●●
●●●●●●
●●
●●
●●●●●●●● ●●●●●●●●●●
●●
●●
●●
●●
●●●●
●●●●●●●●●●●●●●●●●●●●●●
●●
●●●●●●●●●●●●
●●
●●●●●●
●●●●●●
●●●●●●●●●●●●
●●●●●●●●
●●●●
●●●●●●
●●
●●●●●●●●●●●●
●●●●
●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●
●●
●●●●●●●●●●●●
●●●● ●●
●●●●●●●●●●
●● ●●●●
●●●●●●●●●●
●●
●●●●●●
●●●●
●●●●
●●
●●
●●●●
●●●●
●●
●●●●●●
●●●●
●●●●●●
●●●●
●●●●
●●●●●●
●●●●
●●
●●●●●●●●●●●●
●●●●
●●●●●●●●
●●●●
●●●●●●
●●
●●
●●
●●●●●●●●
●●
●●●●
●●
●●
●●●●
●●
●●●●●●●●●●●●
●●
●●
●●●●
●●●●●●●●
●●
●●
●●●●●●●●●●
●●●●
●●
●●
●●
●●●●
●●
●●
●●
●●●●
●●
●●
●●
●●●●●●●●●●●●●●●●●●
●●●●●●●●
●●●● ●●
●●●●
●●●●●●●●●●
●●●●
●●
●●
●●
●●
●●
●●●●●●●●●●●●
●●
●●●●
●●
●●
●●●●●●●●
●●
●●
●●
●●
●● ●●
●●
●●●●●●●●●●
●●●●●●
●●●●●●●●
●●●●
●●
●●●●●● ●●
●●●●
●●
●●
●●
●●
●●●● ●●
●●●●
●●
●●●●●●
●●●●
●●●●●●
●●
●●
●●
●●●●
●●
●●●●●●●●●●
●● ●●●●●●●●
●●
●●
●● ●●
●●●●
●●●●
●●
●●
●●●●●●
●●
●●
●●
●●
●●
●●
●●●●
●●
●●●●●●
●●
●●
●●
●●
●●
●●
●●●●●●●●
●●
●● ●●●●
●●●●
●●●●●●●●
●●●●●●●●
●●
●●●●●●●●
●●●● ●●
●●
●●●●●●●●●●●●●●●●
●●
●●
●●●●
●●
●●
●●●● ●●
●●
●●●●
●●●●●●
●●
●●
●●●●●●●●●●
●●
●●●●●●●●●●●●●●●●●●
●●
●●
●●
●● ●●●●●●
●●
●●
●●●●●●●●●●
●● ●●●●●●
●●
●●
●●
●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●
●●●●
●●●●
●●
●●
●●●●
●●●●●●
●●
●●
●●●●
●●●●●●
●● ●●
●●●●●●●●
●●●●●●●●
●●●●
●●●●
●●
●●●●●●●●●●●●●●●●●●
●●
●●
●●
●●
●●●●
●●●●
●●●●●●●●●●●●●●●● ●●
●●●● ●●
●●●●●●●●
●● ●●
●●●●●●●●
●●
●●●●●●●●●●●●
●●
●●
●● ●●
●●
●●●●
●●
●●●●●●●●●●
●●
●●●●●●
●●
●●
●●
●●
●●
●●●● ●●
●●
●●
●●
●●●●●●
●●●●
●●
●●
●●●●●●
●●●●
●●
●●●●●●●●●●
●●●●●●●●●●●●●●●●●●●●●●●●
●●●●●●●●●●●●●●●●●●●●●●●●
●●
●●●●●●●●●●●●●●
●●●●●●●●
●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●
●●●●●● ●●
●● ●●
●●
●●
●● ●●
●●
●●
●●
●●●●●●
●●●●●●●●●●
●●
●●
●●
●●
●●●●
●●●●
●●
●●
●●
●●
●●
●● ●●
●●
●●●●●●●●●●●●
●●
●●●●
●●
●●●●●●●●●●●●●●●●●●●●●●●●●●●●
●●
●●●●
●● ●●
●●
●●
●● ●●●●●●●●●●●●
●●
●●●●
●●
●●
●●
●●●●
●●
●●●●●●
●●
●●
●● ●●●●●●
●●
●● ●●●●
●●●●
●● ●●
●●●●
●●
●●●●●●
●●
●●●●●●●●
●●
●●●●
●●●●●●
●●
●●
●●●●
●●●●●●
●●
●●
●●
●●●●
●●●●
●●●●
●●
●●
●●
●●●●●●●●●●●●●●●●●●
●●
●●●●●●
●●●●
●●
●●
●●
●●
●●
●●
●●
●●●●
●●●●
●●
●●
●●
●●
●●
●●
●●●●
●●
●●
●●
●●
●●●●●●●●
●●
●●●●●●●●●●●●●●●●●●●●
●●●●
●●
●●●●●●●●●●
●●
●●
●●
●●
●●
●●
●●●●
●●
●●
●●
●●●●●●●●●●●●●●●●
●●
●●
●●●●●●
●●●●
●●●●●●
●● ●●●●●●●●
●●
●●
●●
●●●●●●●●
●●
●●
●●
●●
●●●●●●●●●●●●
●●
●●
●●●●
●●
●●
●●
●●
●●●●●● ●●
●● ●●
●●●●●●●●●●●●●●
●●
●●●●●●●●
●●●●
●●
●●●●●●●●●●
●●
●●●●●●●●●●●●●●●●●●●●●●●●●●●●
●●
●● ●●
●●●●
●● ●● ●●
●●●●●●●● ●●
●●
●●
●●
●●
●●●●●●●●●●●●●●●●●●●●●●
●●
●●
●●●●
●●
●●●●●●
●●●●
●●
●● ●●
●●
●●
●●
●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●
●●
●●●●●●●●●●●●
●●
●●●●●●●●●●
●●
●●
●●●● ●●
●●
●●●●●●
●●
●●
●●
●●●●●●●●●●
●●
●●●●●●●●●●●●●●
●●●●●●
●●
●●
●●
●● ●●
●●●●●●●●●●●●●●●●●●
●●
●●
●●●●●● ●●
●●
●● ●●●●
●●
●●●●●●●●●●●●●●
●●
●●
●●●●
●●
●●●●
●●●●
●●
●●
●●
●●
●●●●●●
●●
●●
●●●●
●●
●●●●●●●●
●●●●●●●●●●●●
●●●●
●● ●●
●●
●●●●●●●●●●●●●●●●
●● ●●
●● ●●
●●
●●
●●●●●●
●●
●●
●● ●●
●●●●
●●
●●
●●●●●●●●
●●
●●●●
●●●●●●
●●●●
●●●●●●●●
●●●●
●●
●●●●●●
●●
●●●●●●●●●●●●●●●●
●●●●
●●
●●●●●●●●●●●●●●
●●
●●●●
●●●●●●
●●
●●●●
●●
●●●●●●●●●●
●● ●●
●●●●●●●●●●●●●●●●
●● ●●
●● ●●
●●
●●●●●●●●
●●●●
●●●●
●●
●●●●
●●●●
●●
●●
●●
●●
●●●●●●●●
●●
●●●●
●●
●●●●●●●●●●●●●●●●●●●●
●●
●●●●●●
●●
●● ●●●●●●●●●●●●●●
●●
●●●●●●●●●●
●●●●●●
●●●●
●●
●●●●
●●
●●●●●●●●●●●●●●
●●
●●
●●●●●●●●
●●
●●●●
●●
●●●●
●●
●●
●●
●●
●●
●●
●●
●●●●●●●●
●●
●●
●●
●●
●●
●●
●●
●●
●●●●●●●●●●
●●
●●
●● ●●
●●
●●
●●
●●
●●
●●●● ●●
●●
●●●●
●●●●
●●●●
●●
●●
●●●●●●
●●
●●
●●
●●●●●●
●●●●●●
●●
●●
●●
●●
●●●●●●
4
5
6
7
8
P = 4.4 x 10-4
2
4
6 ●●
●
●●
●
●
●
●●●●●●●●●●●●
P = 0.015
MEP
EP
IMP
NP
M/D
PreB
HSPC
MkP
2
4
6
8
●
●
P = 4.1 x 10-7
5
6
7
●●●●
P = 0.0019
3
4
5
6
7
8
P = 0.066
3
4
5
6
7
8
●●●
●●●
P = 5.7 x 10-5
2
4
6
●
●
●●
●●●
●●●
●
●●●●●
●●
●
●
●●
●●
●
●●
●●●●
●
●
P = 3.8 x 10−5
● ●
4
5
6
P = 0.78
0
2
4
6
●●
●●●
●
●
●
●●
●
●
●●●
●
P = 0.46
3
5
7 ●
●
●
P = 0.39
0
1
2
3
Module score of MUT/Module score of WTMkPEP NP
P = 0.98
P <10-10
P <10-10
Module
HSPC
b
a
Log
Log
Log
Log
Log
Log
Log
0
2
4
6
8
02468
0
2
4
6
8
02468
0
2
4
6
8
02468
0
2
4
6
8
02468
0
2
4
6
8
02468
0
2
4
6
8
0246 8
0
2
4
6
8
02468
0
2
4
6
8
02468
0
2
4
6
8
02468
0
2
4
6
8
02468
0
2
4
6
8
02468
0
2
4
6
8
02468
0
2
4
6
8
02468
0
2
4
6
8
02468
0
2
4
6
8
02468
0
2
4
6
8
0 246 8
MEP
EP
IMP
NP
M/D
PreB
HSPC
MkP
WT
MUT
WT
MUT
WT
MUT
WT
MUT
WT
MUT
WT
MUT
WT
MUT
WT
MUT
WT MUT
WT MUT
WT MUT
WT MUT
WT MUT
WT MUT
WT MUT
Extended Data Fig. 6 | Cell-cycle module expression in mutant and
wild-type progenitor cells. a, S-phase and G2- and M-phase gene-module
expression in wild-type and mutant cells, in HSPC and MkP clusters from
essential thrombocythaemia samples. Cell-cycle module score represents
the sum of S-phase and G2- and M-phase gene-module expression (two-
sided Wilcoxon rank-sum test; see Methods and Supplementary Table 6
for sample size). Analysis was performed for clusters with at least 20 cells.
b, R atio of committed-progenitor priming-module expression of mutant
and wild-type HSPCs. One mutant and one wild-type HSPC were
randomly sampled from samples ET01–ET05 for each round of analysis
(n = 1,000 iterations, two-sided Wilcoxon rank-sum test).

Nature - USA (2019-07-18)

Get our desktop app

Company

Features

Documentation

Resources