|
| Status |
Public on May 23, 2023 |
| Title |
Systematic screening of chromatin factors identifies divergent roles across haematopoiesis and leukaemia [scRNA-Seq] |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
Cellular differentiation-trajectories require extensive alterations in chromatin structure and function, elicited by a diverse array of chromatin-factors (CFs). Using haematopoiesis as a model-system, we combined bulk ex vivo and single-cell in vivo CRISPR screens to comprehensively characterise the role of CF families in cell-fate decisions. We uncover marked lineage specificities for many CFs, dissecting specific CF-dependencies in vivo at single-cell resolution. This highlights functional diversity among related CFs (i.e. BAF-subcomplexes, MLL-methyltransferases), but also reveals functional redundancy among unrelated Repressive-complexes that restrain excessive myeloid differentiation. Epigenetic-profiling, molecularly explains CF lineage-dependencies, identifying differentiation stage-specific interactions between individual CFs and lineage-determining Transcription Factors (TFs). Intriguingly, non-canonical BAF remodeler disruption abrogates myeloid-TF function generating a pre-leukaemia phenotype. Screening CF functions in leukemia, we show that leukaemia cells abrogate normal CF function, restraining differentiation trajectories by engaging in novel CF-TF interactions that suggest potential therapeutic avenues. Together, our work greatly elucidates the role of CFs and their TF-partners across normal and malignant haematopoiesis.
|
| |
|
| Overall design |
Perturb-seq profiling of CF-KOs in in vivo, ex vivo, and leukemia model systems
|
| |
|
| Contributor(s) |
Lara-Astiaso D, Goñi-Salaverri A, Mendieta-Esteban J, Narayan N, Del Valle C, Gross T, Giotopoulos G, Navarro-Alonso M, Zazpe J, Marchese F, Torrea N, A Calvo I, K Lopez C, Alignani D, Lopez A, Saez B, Taylor-King JP, Prosper F, Fortelny N, Huntly BJ |
| Citation(s) |
37580596 |
| |
| Submission date |
Sep 16, 2022 |
| Last update date |
Aug 22, 2023 |
| Contact name |
Brian Huntly |
| E-mail(s) |
bjph2@cam.ac.uk
|
| Organization name |
University of Cambridge
|
| Department |
Department of Haematology
|
| Street address |
Hills Road
|
| City |
Cambridge |
| ZIP/Postal code |
CB2 0AW |
| Country |
United Kingdom |
| |
|
| Platforms (2) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
| GPL30172 |
NextSeq 2000 (Mus musculus) |
|
| Samples (68)
|
|
| This SubSeries is part of SuperSeries: |
|
| Relations |
| BioProject |
PRJNA881278 |
| SRA |
SRP397634 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE213511_CellAnnotation_exvivo.tsv.gz |
2.8 Mb |
(ftp)(http) |
TSV |
| GSE213511_CellAnnotation_invivo.tsv.gz |
2.0 Mb |
(ftp)(http) |
TSV |
| GSE213511_CellAnnotation_leukemia.tsv.gz |
1.7 Mb |
(ftp)(http) |
TSV |
| GSE213511_DM_CITEseq-1_NA_NM_1.h5 |
40.5 Mb |
(ftp)(http) |
H5 |
| GSE213511_DM_CITEseq-2_NA_NM_1.h5 |
42.2 Mb |
(ftp)(http) |
H5 |
| GSE213511_DM_OP0_NM_6d_1.h5 |
55.2 Mb |
(ftp)(http) |
H5 |
| GSE213511_DM_OP1_NM_6d_1.h5 |
79.4 Mb |
(ftp)(http) |
H5 |
| GSE213511_DM_OP1_NM_6d_2.h5 |
84.4 Mb |
(ftp)(http) |
H5 |
| GSE213511_DM_OP2_NM_6d_1.h5 |
74.0 Mb |
(ftp)(http) |
H5 |
| GSE213511_DM_OP2_NM_6d_2.h5 |
49.7 Mb |
(ftp)(http) |
H5 |
| GSE213511_DM_OP2_NM_6d_3.h5 |
45.5 Mb |
(ftp)(http) |
H5 |
| GSE213511_DM_OP3_NM_6d_1.h5 |
48.3 Mb |
(ftp)(http) |
H5 |
| GSE213511_DM_OP4_NM_6d_1.h5 |
50.8 Mb |
(ftp)(http) |
H5 |
| GSE213511_DM_OP5_NM_6d_1.h5 |
32.1 Mb |
(ftp)(http) |
H5 |
| GSE213511_DM_Test1_NM_6d_1.h5 |
51.6 Mb |
(ftp)(http) |
H5 |
| GSE213511_DM_Test2_NM_6d_1.h5 |
10.8 Mb |
(ftp)(http) |
H5 |
| GSE213511_LSK_OP0_NM_7d_1.h5 |
60.0 Mb |
(ftp)(http) |
H5 |
| GSE213511_LSK_OP1_NM_7d_1.h5 |
66.0 Mb |
(ftp)(http) |
H5 |
| GSE213511_LSK_OP1_NM_9d_1.h5 |
84.7 Mb |
(ftp)(http) |
H5 |
| GSE213511_LSK_OP2_NM_7d_1.h5 |
57.6 Mb |
(ftp)(http) |
H5 |
| GSE213511_LSK_OP2_NM_9d_1.h5 |
70.3 Mb |
(ftp)(http) |
H5 |
| GSE213511_LSK_OP3_NM_7d_1.h5 |
78.4 Mb |
(ftp)(http) |
H5 |
| GSE213511_LSK_OP3_NM_9d_1.h5 |
89.3 Mb |
(ftp)(http) |
H5 |
| GSE213511_LSK_OP4_NM_7d_1.h5 |
61.4 Mb |
(ftp)(http) |
H5 |
| GSE213511_LSK_OP4_NM_9d_1.h5 |
54.8 Mb |
(ftp)(http) |
H5 |
| GSE213511_inVivo_NTC_lin-andckit_14d_1.h5 |
12.0 Mb |
(ftp)(http) |
H5 |
| GSE213511_inVivo_OP1_ckit_14d_1.h5 |
27.1 Mb |
(ftp)(http) |
H5 |
| GSE213511_inVivo_OP1_lin-_14d_1.h5 |
73.0 Mb |
(ftp)(http) |
H5 |
| GSE213511_inVivo_OP1_lin-_14d_2.h5 |
17.4 Mb |
(ftp)(http) |
H5 |
| GSE213511_inVivo_OP1_lin-_28d_1.h5 |
53.9 Mb |
(ftp)(http) |
H5 |
| GSE213511_inVivo_OP1_lin-_28d_2.h5 |
25.5 Mb |
(ftp)(http) |
H5 |
| GSE213511_inVivo_OP2_ckit_14d_1.h5 |
30.6 Mb |
(ftp)(http) |
H5 |
| GSE213511_inVivo_OP2_lin-_14d_1.h5 |
55.2 Mb |
(ftp)(http) |
H5 |
| GSE213511_inVivo_OP3_ckit_14d_1.h5 |
38.5 Mb |
(ftp)(http) |
H5 |
| GSE213511_inVivo_OP3_lin-_14d_1.h5 |
64.3 Mb |
(ftp)(http) |
H5 |
| GSE213511_inVivo_OP4_ckit_14d_1.h5 |
17.3 Mb |
(ftp)(http) |
H5 |
| GSE213511_inVivo_OP4_lin-_14d_1.h5 |
20.6 Mb |
(ftp)(http) |
H5 |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
Less...
More...