PTEN regulates hematopoietic lineage plasticity via PU.1-dependent chromatin accessibility.
PTEN loss in fetal liver hematopoietic stem cells (HSCs) leads to alterations in myeloid, T-, and B-lineage potentials and T-lineage acute lymphoblastic leukemia (T-ALL) development. To explore the mechanism underlying PTEN-regulated hematopoietic lineage choices, we carry out integrated assay for transposase-accessible chromatin using sequencing (ATAC-seq), single-cell RNA-seq, and in vitro culture analyses using in vivo-isolated mouse pre-leukemic HSCs and progenitors. We find that PTEN loss alters chromatin accessibility of key lineage transcription factor (TF) binding sites at the prepro-B stage, corresponding to increased myeloid and T-lineage potentials and reduced B-lineage potential. Importantly, we find that PU.1 is an essential TF downstream of PTEN and that altering PU.1 levels can reprogram the chromatin accessibility landscape and myeloid, T-, and B-lineage potentials in Ptennull prepro-B cells. Our study discovers prepro-B as the key developmental stage underlying PTEN-regulated hematopoietic lineage choices and suggests a critical role of PU.1 in modulating the epigenetic state and lineage plasticity of prepro-B progenitors.
Pubmed ID: 37561626 RIS Download
Research resources used in this publication
- OP9/G-DLL1 (RRID:CVCL_B218) (cell line)
- OP9 (RRID:CVCL_4398) (cell line)
- OP9/G-DLL1 (RRID:CVCL_B218) (cell line)
- OP9 (RRID:CVCL_4398) (cell line)
- Fluorescein (FITC)-AffiniPure Fab Fragment Donkey Anti-Rabbit IgG (H+L) (RRID:AB_2340598) (antibody)
- PU.1 (9G7) Rabbit mAb (RRID:AB_2186909) (antibody)
- APC/Cyanine7 anti-mouse TER-119/Erythroid Cells (RRID:AB_2137788) (antibody)
- FITC anti-mouse Siglec H (RRID:AB_1227761) (antibody)
- APC/Cyanine7 anti-mouse Ly-6G/Ly-6C (Gr-1) (RRID:AB_2137485) (antibody)
- APC anti-mouse Ly-6G/Ly-6C (Gr-1) (RRID:AB_313377) (antibody)
- PE/Cyanine7 anti-mouse Ly-6A/E (Sca-1) (RRID:AB_756199) (antibody)
- IgM (RRID:AB_398464) (antibody)
- CD8a Monoclonal Antibody (53-6.7), PerCP-Cyanine5.5, eBioscience (RRID:AB_1107004) (antibody)
- APC/Cyanine7 anti-mouse/human CD45R/B220 (RRID:AB_313007) (antibody)
- Brilliant Violet 510(TM) anti-mouse CD48 (RRID:AB_2650826) (antibody)
- Brilliant Violet 605(TM) anti-mouse/human CD45R/B220 (RRID:AB_2563312) (antibody)
- CD45R/B220 (RRID:AB_394615) (antibody)
- Brilliant Violet 510(TM) anti-mouse CD45 (RRID:AB_2563061) (antibody)
- APC anti-mouse CD45 (RRID:AB_312977) (antibody)
- CD45 (RRID:AB_2737976) (antibody)
- CD43 Monoclonal Antibody (eBioR2/60), FITC, eBioscience (RRID:AB_465040) (antibody)
- APC anti-mouse CD43 (RRID:AB_11149685) (antibody)
- CD4 Monoclonal Antibody (RM4-5), FITC, eBioscience (RRID:AB_464896) (antibody)
- APC/Cyanine7 anti-mouse CD4 (RRID:AB_312699) (antibody)
- CD4 (RRID:AB_394331) (antibody)
- APC/Cyanine7 anti-mouse CD3epsilon (RRID:AB_1877170) (antibody)
- PE/Cyanine7 anti-mouse CD3epsilon (RRID:AB_312685) (antibody)
- Armenian Hamster Anti-CD3e Monoclonal Antibody, Biotin Conjugated, Clone 145-2C11 (RRID:AB_394592) (antibody)
- CD38 Monoclonal Antibody (90), Alexa Fluor™ 700, eBioscience (RRID:AB_657740) (antibody)
- Pacific Blue(TM) anti-mouse CD38 (RRID:AB_10613468) (antibody)
- PE/Cyanine7 anti-mouse CD38 (RRID:AB_2275531) (antibody)
- APC anti-mouse CD38 (RRID:AB_312933) (antibody)
- Rat Anti-Mouse CD34 Monoclonal Antibody, FITC Conjugated (RRID:AB_1645242) (antibody)
- CD34 (RRID:AB_1727471) (antibody)
- PE/Cyanine7 anti-mouse CD25 (RRID:AB_312865) (antibody)
- Rat Anti-Mouse CD16 / CD32 Antibody, V450 Conjugated (RRID:AB_1645268) (antibody)
- PE/Cyanine7 anti-mouse CD19 (RRID:AB_313655) (antibody)
- Pacific Blue(TM) anti-mouse CD150 (SLAM) (RRID:AB_2270307) (antibody)
- CD135 (FLT3) (RRID:AB_2737876) (antibody)
- FITC anti-mouse CD127 (IL-7Ralpha) (RRID:AB_1937231) (antibody)
- APC/Cyanine7 anti-mouse CD11c (RRID:AB_830646) (antibody)
- APC anti-mouse CD11c (RRID:AB_313778) (antibody)
- CD11c (RRID:AB_395060) (antibody)
- CD11c (RRID:AB_10611727) (antibody)
- APC/Cyanine7 anti-mouse/human CD11b (RRID:AB_830642) (antibody)
- CD11b (RRID:AB_10897015) (antibody)
- APC anti-mouse CD117 (c-kit) (RRID:AB_313221) (antibody)
- CD11b (Integrin a M chain) (RRID:AB_2296385) (antibody)
Additional research tools detected in this publication
None foundAntibodies used in this publication
- APC/Cyanine7 anti-mouse TER-119/Erythroid Cells (RRID:AB_2137788)
- FITC anti-mouse Siglec H (RRID:AB_1227761)
- APC/Cyanine7 anti-mouse Ly-6G/Ly-6C (Gr-1) (RRID:AB_2137485)
- APC anti-mouse Ly-6G/Ly-6C (Gr-1) (RRID:AB_313377)
- PE/Cyanine7 anti-mouse Ly-6A/E (Sca-1) (RRID:AB_756199)
- CD8a Monoclonal Antibody (53-6.7), PerCP-Cyanine5.5, eBioscience (RRID:AB_1107004)
- IgM (RRID:AB_398464)
- APC/Cyanine7 anti-mouse/human CD45R/B220 (RRID:AB_313007)
- Brilliant Violet 510(TM) anti-mouse CD48 (RRID:AB_2650826)
- CD45 (RRID:AB_2737976)
- CD43 Monoclonal Antibody (eBioR2/60), FITC, eBioscience (RRID:AB_465040)
- APC anti-mouse CD43 (RRID:AB_11149685)
- CD4 Monoclonal Antibody (RM4-5), FITC, eBioscience (RRID:AB_464896)
- Armenian Hamster Anti-CD3e Monoclonal Antibody, Biotin Conjugated, Clone 145-2C11 (RRID:AB_394592)
- CD38 Monoclonal Antibody (90), Alexa Fluor™ 700, eBioscience (RRID:AB_657740)
- Pacific Blue(TM) anti-mouse CD38 (RRID:AB_10613468)
- Rat Anti-Mouse CD34 Monoclonal Antibody, FITC Conjugated (RRID:AB_1645242)
- Brilliant Violet 605(TM) anti-mouse/human CD45R/B220 (RRID:AB_2563312)
- CD45R/B220 (RRID:AB_394615)
- Brilliant Violet 510(TM) anti-mouse CD45 (RRID:AB_2563061)
- APC anti-mouse CD45 (RRID:AB_312977)
- APC/Cyanine7 anti-mouse CD4 (RRID:AB_312699)
- CD4 (RRID:AB_394331)
- APC/Cyanine7 anti-mouse CD3epsilon (RRID:AB_1877170)
- PE/Cyanine7 anti-mouse CD3epsilon (RRID:AB_312685)
- PE/Cyanine7 anti-mouse CD25 (RRID:AB_312865)
- CD34 (RRID:AB_1727471)
- Rat Anti-Mouse CD16 / CD32 Antibody, V450 Conjugated (RRID:AB_1645268)
- Pacific Blue(TM) anti-mouse CD150 (SLAM) (RRID:AB_2270307)
- CD135 (FLT3) (RRID:AB_2737876)
- FITC anti-mouse CD127 (IL-7Ralpha) (RRID:AB_1937231)
- APC/Cyanine7 anti-mouse CD11c (RRID:AB_830646)
- APC anti-mouse CD11c (RRID:AB_313778)
- CD11c (RRID:AB_10611727)
- APC/Cyanine7 anti-mouse/human CD11b (RRID:AB_830642)
- CD11b (RRID:AB_10897015)
- CD11b (Integrin a M chain) (RRID:AB_2296385)
- PU.1 (9G7) Rabbit mAb (RRID:AB_2186909)
- Fluorescein (FITC)-AffiniPure Fab Fragment Donkey Anti-Rabbit IgG (H+L) (RRID:AB_2340598)
- PE/Cyanine7 anti-mouse CD38 (RRID:AB_2275531)
- APC anti-mouse CD38 (RRID:AB_312933)
- PE/Cyanine7 anti-mouse CD19 (RRID:AB_313655)
- CD11c (RRID:AB_395060)
- APC anti-mouse CD117 (c-kit) (RRID:AB_313221)
Associated grants
NonePublication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.
This is a list of tools and resources that we have found mentioned in this publication.
APC/Cyanine7 anti-mouse TER-119/Erythroid Cells (antibody)
RRID:AB_2137788
This monoclonal targets TER-119
View all literature mentionsFITC anti-mouse Siglec H (antibody)
RRID:AB_1227761
This monoclonal targets Siglec H
View all literature mentionsAPC/Cyanine7 anti-mouse Ly-6G/Ly-6C (Gr-1) (antibody)
RRID:AB_2137485
This monoclonal targets Ly-6G Ly-6C
View all literature mentionsAPC anti-mouse Ly-6G/Ly-6C (Gr-1) (antibody)
RRID:AB_313377
This monoclonal targets Ly-6G Ly-6C
View all literature mentionsPE/Cyanine7 anti-mouse Ly-6A/E (Sca-1) (antibody)
RRID:AB_756199
This monoclonal targets Ly-6A/E
View all literature mentionsCD8a Monoclonal Antibody (53-6.7), PerCP-Cyanine5.5, eBioscience (antibody)
RRID:AB_1107004
This monoclonal targets CD8a
View all literature mentionsAPC/Cyanine7 anti-mouse/human CD45R/B220 (antibody)
RRID:AB_313007
This monoclonal targets CD45R
View all literature mentionsBrilliant Violet 510(TM) anti-mouse CD48 (antibody)
RRID:AB_2650826
This monoclonal targets CD48
View all literature mentionsCD43 Monoclonal Antibody (eBioR2/60), FITC, eBioscience (antibody)
RRID:AB_465040
This monoclonal targets CD43
View all literature mentionsAPC anti-mouse CD43 (antibody)
RRID:AB_11149685
This monoclonal targets CD43
View all literature mentionsCD4 Monoclonal Antibody (RM4-5), FITC, eBioscience (antibody)
RRID:AB_464896
This monoclonal targets CD4
View all literature mentionsArmenian Hamster Anti-CD3e Monoclonal Antibody, Biotin Conjugated, Clone 145-2C11 (antibody)
RRID:AB_394592
This monoclonal targets CD3e
View all literature mentionsCD38 Monoclonal Antibody (90), Alexa Fluor™ 700, eBioscience (antibody)
RRID:AB_657740
This monoclonal targets CD38
View all literature mentionsPacific Blue(TM) anti-mouse CD38 (antibody)
RRID:AB_10613468
This monoclonal targets CD38
View all literature mentionsRat Anti-Mouse CD34 Monoclonal Antibody, FITC Conjugated (antibody)
RRID:AB_1645242
This monoclonal targets Mouse CD34
View all literature mentionsBrilliant Violet 605(TM) anti-mouse/human CD45R/B220 (antibody)
RRID:AB_2563312
This monoclonal targets CD45R
View all literature mentionsCD45R/B220 (antibody)
RRID:AB_394615
This monoclonal targets CD45R / B220
View all literature mentionsBrilliant Violet 510(TM) anti-mouse CD45 (antibody)
RRID:AB_2563061
This monoclonal targets CD45
View all literature mentionsAPC anti-mouse CD45 (antibody)
RRID:AB_312977
This monoclonal targets CD45
View all literature mentionsAPC/Cyanine7 anti-mouse CD4 (antibody)
RRID:AB_312699
This monoclonal targets CD4
View all literature mentionsAPC/Cyanine7 anti-mouse CD3epsilon (antibody)
RRID:AB_1877170
This monoclonal targets CD3epsilon
View all literature mentionsPE/Cyanine7 anti-mouse CD3epsilon (antibody)
RRID:AB_312685
This monoclonal targets CD3epsilon
View all literature mentionsPE/Cyanine7 anti-mouse CD25 (antibody)
RRID:AB_312865
This monoclonal targets CD25
View all literature mentionsRat Anti-Mouse CD16 / CD32 Antibody, V450 Conjugated (antibody)
RRID:AB_1645268
This unknown targets CD16/CD32
View all literature mentionsPacific Blue(TM) anti-mouse CD150 (SLAM) (antibody)
RRID:AB_2270307
This monoclonal targets CD150
View all literature mentionsCD135 (FLT3) (antibody)
RRID:AB_2737876
This monoclonal targets CD135 (FLT3)
View all literature mentionsFITC anti-mouse CD127 (IL-7Ralpha) (antibody)
RRID:AB_1937231
This monoclonal targets CD127
View all literature mentionsAPC/Cyanine7 anti-mouse CD11c (antibody)
RRID:AB_830646
This monoclonal targets CD11c
View all literature mentionsAPC anti-mouse CD11c (antibody)
RRID:AB_313778
This monoclonal targets CD11c
View all literature mentionsAPC/Cyanine7 anti-mouse/human CD11b (antibody)
RRID:AB_830642
This monoclonal targets CD11b
View all literature mentionsCD11b (Integrin a M chain) (antibody)
RRID:AB_2296385
This monoclonal targets Itgam
View all literature mentionsPU.1 (9G7) Rabbit mAb (antibody)
RRID:AB_2186909
This monoclonal targets Sfpi1
View all literature mentionsFluorescein (FITC)-AffiniPure Fab Fragment Donkey Anti-Rabbit IgG (H+L) (antibody)
RRID:AB_2340598
This unknown targets Rabbit IgG (H+L)
View all literature mentionsPE/Cyanine7 anti-mouse CD38 (antibody)
RRID:AB_2275531
This monoclonal targets CD38
View all literature mentionsAPC anti-mouse CD38 (antibody)
RRID:AB_312933
This monoclonal targets CD38
View all literature mentionsPE/Cyanine7 anti-mouse CD19 (antibody)
RRID:AB_313655
This monoclonal targets CD19
View all literature mentionsAPC anti-mouse CD117 (c-kit) (antibody)
RRID:AB_313221
This monoclonal targets CD117
View all literature mentionsOP9/G-DLL1 (cell line)
RRID:CVCL_B218
Cell line OP9/G-DLL1 is a Stromal cell line with a species of origin Mus musculus (Mouse)
View all literature mentionsOP9 (cell line)
RRID:CVCL_4398
Cell line OP9 is a Stromal cell line with a species of origin Mus musculus
View all literature mentionsOP9/G-DLL1 (cell line)
RRID:CVCL_B218
Cell line OP9/G-DLL1 is a Stromal cell line with a species of origin Mus musculus (Mouse)
View all literature mentionsOP9 (cell line)
RRID:CVCL_4398
Cell line OP9 is a Stromal cell line with a species of origin Mus musculus
View all literature mentionsFluorescein (FITC)-AffiniPure Fab Fragment Donkey Anti-Rabbit IgG (H+L) (antibody)
RRID:AB_2340598
This unknown targets Rabbit IgG (H+L)
View all literature mentionsPU.1 (9G7) Rabbit mAb (antibody)
RRID:AB_2186909
This monoclonal targets Sfpi1
View all literature mentionsAPC/Cyanine7 anti-mouse TER-119/Erythroid Cells (antibody)
RRID:AB_2137788
This monoclonal targets TER-119
View all literature mentionsFITC anti-mouse Siglec H (antibody)
RRID:AB_1227761
This monoclonal targets Siglec H
View all literature mentionsAPC/Cyanine7 anti-mouse Ly-6G/Ly-6C (Gr-1) (antibody)
RRID:AB_2137485
This monoclonal targets Ly-6G Ly-6C
View all literature mentionsAPC anti-mouse Ly-6G/Ly-6C (Gr-1) (antibody)
RRID:AB_313377
This monoclonal targets Ly-6G Ly-6C
View all literature mentionsPE/Cyanine7 anti-mouse Ly-6A/E (Sca-1) (antibody)
RRID:AB_756199
This monoclonal targets Ly-6A/E
View all literature mentionsCD8a Monoclonal Antibody (53-6.7), PerCP-Cyanine5.5, eBioscience (antibody)
RRID:AB_1107004
This monoclonal targets CD8a
View all literature mentionsAPC/Cyanine7 anti-mouse/human CD45R/B220 (antibody)
RRID:AB_313007
This monoclonal targets CD45R
View all literature mentionsBrilliant Violet 510(TM) anti-mouse CD48 (antibody)
RRID:AB_2650826
This monoclonal targets CD48
View all literature mentionsBrilliant Violet 605(TM) anti-mouse/human CD45R/B220 (antibody)
RRID:AB_2563312
This monoclonal targets CD45R
View all literature mentionsCD45R/B220 (antibody)
RRID:AB_394615
This monoclonal targets CD45R / B220
View all literature mentionsBrilliant Violet 510(TM) anti-mouse CD45 (antibody)
RRID:AB_2563061
This monoclonal targets CD45
View all literature mentionsAPC anti-mouse CD45 (antibody)
RRID:AB_312977
This monoclonal targets CD45
View all literature mentionsCD43 Monoclonal Antibody (eBioR2/60), FITC, eBioscience (antibody)
RRID:AB_465040
This monoclonal targets CD43
View all literature mentionsAPC anti-mouse CD43 (antibody)
RRID:AB_11149685
This monoclonal targets CD43
View all literature mentionsCD4 Monoclonal Antibody (RM4-5), FITC, eBioscience (antibody)
RRID:AB_464896
This monoclonal targets CD4
View all literature mentionsAPC/Cyanine7 anti-mouse CD4 (antibody)
RRID:AB_312699
This monoclonal targets CD4
View all literature mentionsAPC/Cyanine7 anti-mouse CD3epsilon (antibody)
RRID:AB_1877170
This monoclonal targets CD3epsilon
View all literature mentionsPE/Cyanine7 anti-mouse CD3epsilon (antibody)
RRID:AB_312685
This monoclonal targets CD3epsilon
View all literature mentionsArmenian Hamster Anti-CD3e Monoclonal Antibody, Biotin Conjugated, Clone 145-2C11 (antibody)
RRID:AB_394592
This monoclonal targets CD3e
View all literature mentionsCD38 Monoclonal Antibody (90), Alexa Fluor™ 700, eBioscience (antibody)
RRID:AB_657740
This monoclonal targets CD38
View all literature mentionsPacific Blue(TM) anti-mouse CD38 (antibody)
RRID:AB_10613468
This monoclonal targets CD38
View all literature mentionsPE/Cyanine7 anti-mouse CD38 (antibody)
RRID:AB_2275531
This monoclonal targets CD38
View all literature mentionsAPC anti-mouse CD38 (antibody)
RRID:AB_312933
This monoclonal targets CD38
View all literature mentionsRat Anti-Mouse CD34 Monoclonal Antibody, FITC Conjugated (antibody)
RRID:AB_1645242
This monoclonal targets Mouse CD34
View all literature mentionsPE/Cyanine7 anti-mouse CD25 (antibody)
RRID:AB_312865
This monoclonal targets CD25
View all literature mentionsRat Anti-Mouse CD16 / CD32 Antibody, V450 Conjugated (antibody)
RRID:AB_1645268
This unknown targets CD16/CD32
View all literature mentionsPE/Cyanine7 anti-mouse CD19 (antibody)
RRID:AB_313655
This monoclonal targets CD19
View all literature mentionsPacific Blue(TM) anti-mouse CD150 (SLAM) (antibody)
RRID:AB_2270307
This monoclonal targets CD150
View all literature mentionsCD135 (FLT3) (antibody)
RRID:AB_2737876
This monoclonal targets CD135 (FLT3)
View all literature mentionsFITC anti-mouse CD127 (IL-7Ralpha) (antibody)
RRID:AB_1937231
This monoclonal targets CD127
View all literature mentionsAPC/Cyanine7 anti-mouse CD11c (antibody)
RRID:AB_830646
This monoclonal targets CD11c
View all literature mentionsAPC anti-mouse CD11c (antibody)
RRID:AB_313778
This monoclonal targets CD11c
View all literature mentionsAPC/Cyanine7 anti-mouse/human CD11b (antibody)
RRID:AB_830642
This monoclonal targets CD11b
View all literature mentionsAPC anti-mouse CD117 (c-kit) (antibody)
RRID:AB_313221
This monoclonal targets CD117
View all literature mentionsCD11b (Integrin a M chain) (antibody)
RRID:AB_2296385
This monoclonal targets Itgam
View all literature mentions
