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GEO help: Mouse over screen elements for information. |
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| Status |
Public on May 02, 2023 |
| Title |
Massively parallel base editing to map variant effects in human hematopoiesis |
| Organisms |
Homo sapiens; Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Systematic evaluation of the impact of genetic variants is critical for the study and treatment of human physiology and disease. While specific mutations can be introduced by genome engineering, we still lack scalable approaches that are applicable to the important setting of primary cells, such as blood and immune cells. Here, we describe the development of massively parallel base-editing screens in human hematopoietic stem and progenitor cells. Such approaches enable functional screens for variant effects across any hematopoietic differentiation state. Moreover, they allow rich phenotyping through single-cell RNA sequencing readouts, and separately, characterization of editing outcomes through pooled single-cell genotyping. We efficiently design improved leukemia immunotherapy approaches, comprehensively identify non-coding variants modulating fetal hemoglobin expression, define mechanisms regulating hematopoietic differentiation, and probe the pathogenicity of uncharacterized disease-associated variants. These strategies will advance effective and high-throughput variant-to-function mapping in human hematopoiesis to identify the causes of diverse diseases.
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| Overall design |
Hematopoietic stem and progenitor cells transduced with lentiviruses expressing pooled library sgRNAs were electroporated with high purity genome editor protein
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| Contributor(s) |
Martin-Rufino JD, Sankaran VG |
| Citation(s) |
37137305 |
| Submission date |
Oct 11, 2022 |
| Last update date |
Aug 01, 2023 |
| Contact name |
Jorge Diego Martin Rufino |
| Organization name |
Harvard University / Broad Institute of MIT and Harvard / Boston Children's Hospital
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| Street address |
415 Main Street
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| City |
Cambridge |
| State/province |
MA |
| ZIP/Postal code |
02142 |
| Country |
USA |
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| Platforms (4)
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| GPL18573 |
Illumina NextSeq 500 (Homo sapiens) |
| GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
| GPL30173 |
NextSeq 2000 (Homo sapiens) |
| GPL30202 |
NextSeq 2000 (Homo sapiens; Mus musculus) |
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| Samples (106)
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| GSM6630380 |
Differentiated HSPCs, 4 arrayed lentiviruses, rep 1, scRNA-seq |
| GSM6630381 |
Differentiated HSPCs, 4 arrayed lentiviruses, rep 1, barcoded antibody (ADT) |
| GSM6630382 |
Differentiated HSPCs, 4 arrayed lentiviruses, rep 1, enrichment PCR |
| GSM6630383 |
Differentiated HSPCs, 4 arrayed lentiviruses, rep 2, scRNA-seq |
| GSM6630384 |
Differentiated HSPCs, 4 arrayed lentiviruses, rep 2, barcoded antibody (ADT) |
| GSM6630385 |
Differentiated HSPCs, 4 arrayed lentiviruses, rep 2, enrichment PCR |
| GSM7110803 |
HSPC-derived erythroblasts, HBG1/2 library, rep1, scRNA-seq |
| GSM7110804 |
HSPC-derived erythroblasts, HBG1/2 library, rep1, enrichment PCR |
| GSM7110805 |
HSPC-derived erythroblasts, HBG1/2 library, rep2, scRNA-seq |
| GSM7110806 |
HSPC-derived erythroblasts, HBG1/2 library, rep2, enrichment PCR |
| GSM7110807 |
HSPC-derived erythroblasts, HBG1/2 library, rep3, scRNA-seq |
| GSM7110808 |
HSPC-derived erythroblasts, HBG1/2 library, rep3, enrichment PCR |
| GSM7110809 |
HSPC-derived erythroblasts, HBG1/2 library, rep4, scRNA-seq |
| GSM7110810 |
HSPC-derived erythroblasts, HBG1/2 library, rep4, enrichment PCR |
| GSM7110811 |
HSPC-derived erythroblasts, HBG1/2 library, rep5, scRNA-seq |
| GSM7110812 |
HSPC-derived erythroblasts, HBG1/2 library, rep5, enrichment PCR |
| GSM7110813 |
HSPC-derived erythroblasts, HBG1/2 library, rep6, scRNA-seq |
| GSM7110814 |
HSPC-derived erythroblasts, HBG1/2 library, rep6, enrichment PCR |
| GSM7110815 |
HSPC-derived erythroblasts, edited with HBG1/2 library, rep7, scRNA-seq |
| GSM7110816 |
HSPC-derived erythroblasts, edited with HBG1/2 library, rep7, enrichment PCR |
| GSM7110817 |
HSPC-derived erythroblasts, edited with HBG1/2 library, rep8, scRNA-seq |
| GSM7110818 |
HSPC-derived erythroblasts, edited with HBG1/2 library, rep8, enrichment PCR |
| GSM7110819 |
Differentiated HSPCs day 2 erythroid, GATA1 library, rep1, scRNA-seq |
| GSM7110820 |
Differentiated HSPCs day 2 erythroid, GATA1 library, rep1, enrichment PCR |
| GSM7110821 |
Differentiated HSPCs day 2 erythroid, GATA1 library, rep2, scRNA-seq |
| GSM7110822 |
Differentiated HSPCs day 2 erythroid, GATA1 library, rep2, enrichment PCR |
| GSM7110823 |
Differentiated HSPCs day 2 erythroid, GATA1 library, rep3, scRNA-seq |
| GSM7110824 |
Differentiated HSPCs day 2 erythroid, GATA1 library, rep3, enrichment PCR |
| GSM7110825 |
Differentiated HSPCs day 2 erythroid, GATA1 library, rep4, scRNA-seq |
| GSM7110826 |
Differentiated HSPCs day 2 erythroid, GATA1 library, rep4, enrichment PCR |
| GSM7110827 |
Differentiated HSPCs day 2 erythroid, GATA1 library, rep5, scRNA-seq |
| GSM7110828 |
Differentiated HSPCs day 2 erythroid, GATA1 library, rep5, enrichment PCR |
| GSM7110829 |
Differentiated HSPCs day 2 erythroid, GATA1 library, rep6, scRNA-seq |
| GSM7110830 |
Differentiated HSPCs day 2 erythroid, GATA1 library, rep6, enrichment PCR |
| GSM7110831 |
Differentiated HSPCs day 2 erythroid, GATA1 library, rep7, scRNA-seq |
| GSM7110832 |
Differentiated HSPCs day 2 erythroid, GATA1 library, rep7, enrichment PCR |
| GSM7110833 |
Differentiated HSPCs day 2 erythroid, GATA1 library, rep8, scRNA-seq |
| GSM7110834 |
Differentiated HSPCs day 2 erythroid, GATA1 library, rep8, enrichment PCR |
| GSM7110835 |
Differentiated HSPCs day 4 erythroid, GATA1 library, rep9, scRNA-seq |
| GSM7110836 |
Differentiated HSPCs day 4 erythroid, GATA1 library, rep9, enrichment PCR |
| GSM7110837 |
Differentiated HSPCs day 4 erythroid, GATA1 library, rep10, scRNA-seq |
| GSM7110838 |
Differentiated HSPCs day 4 erythroid, GATA1 library, rep10, enrichment PCR |
| GSM7110839 |
Differentiated HSPCs day 4 erythroid, GATA1 library, rep11, scRNA-seq |
| GSM7110840 |
Differentiated HSPCs day 4 erythroid, GATA1 library, rep11, enrichment PCR |
| GSM7110841 |
Differentiated HSPCs day 4 erythroid, GATA1 library, rep12, scRNA-seq |
| GSM7110842 |
Differentiated HSPCs day 4 erythroid, GATA1 library, rep12, enrichment PCR |
| GSM7110843 |
Differentiated HSPCs day 4 erythroid, GATA1 library, rep13, scRNA-seq |
| GSM7110844 |
Differentiated HSPCs day 4 erythroid, GATA1 library, rep13, enrichment PCR |
| GSM7110845 |
Differentiated HSPCs day 4 erythroid, GATA1 library, rep14, scRNA-seq |
| GSM7110846 |
Differentiated HSPCs day 4 erythroid, GATA1 library, rep14, enrichment PCR |
| GSM7110847 |
Differentiated HSPCs day 4 erythroid, GATA1 library, rep15, scRNA-seq |
| GSM7110848 |
Differentiated HSPCs day 4 erythroid, GATA1 library, rep15, enrichment PCR |
| GSM7110849 |
Differentiated HSPCs day 7 erythroid, GATA1 library, rep17, scRNA-seq |
| GSM7110850 |
Differentiated HSPCs day 7 erythroid, GATA1 library, rep17, enrichment PCR |
| GSM7110851 |
Differentiated HSPCs day 7 erythroid, GATA1 library, rep18, scRNA-seq |
| GSM7110852 |
Differentiated HSPCs day 7 erythroid, GATA1 library, rep18, enrichment PCR |
| GSM7110853 |
Differentiated HSPCs day 7 erythroid, GATA1 library, rep19, scRNA-seq |
| GSM7110854 |
Differentiated HSPCs day 7 erythroid, GATA1 library, rep19, enrichment PCR |
| GSM7110855 |
Differentiated HSPCs day 7 erythroid, GATA1 library, rep20, scRNA-seq |
| GSM7110856 |
Differentiated HSPCs day 7 erythroid, GATA1 library, rep20, enrichment PCR |
| GSM7110857 |
Differentiated HSPCs day 7 erythroid, GATA1 library, rep21, scRNA-seq |
| GSM7110858 |
Differentiated HSPCs day 7 erythroid, GATA1 library, rep21, enrichment PCR |
| GSM7110859 |
Differentiated HSPCs day 7 erythroid, GATA1 library, rep22, scRNA-seq |
| GSM7110860 |
Differentiated HSPCs day 7 erythroid, GATA1 library, rep22, enrichment PCR |
| GSM7110861 |
Differentiated HSPCs day 7 erythroid, GATA1 library, rep23, scRNA-seq |
| GSM7110862 |
Differentiated HSPCs day 7 erythroid, GATA1 library, rep23, enrichment PCR |
| GSM7110863 |
Differentiated HSPCs day 7 erythroid, GATA1 library, rep24, scRNA-seq |
| GSM7110864 |
Differentiated HSPCs day 7 erythroid, GATA1 library, rep24, enrichment PCR |
| GSM7110865 |
Differentiated HSPCs day 9 erythroid, GATA1 library, rep25, scRNA-seq |
| GSM7110866 |
Differentiated HSPCs day 9 erythroid, GATA1 library, rep25, enrichment PCR |
| GSM7110867 |
Differentiated HSPCs day 9 erythroid, GATA1 library, rep26, scRNA-seq |
| GSM7110868 |
Differentiated HSPCs day 9 erythroid, GATA1 library, rep26, enrichment PCR |
| GSM7110869 |
Differentiated HSPCs day 9 erythroid, GATA1 library, rep27, scRNA-seq |
| GSM7110870 |
Differentiated HSPCs day 9 erythroid, GATA1 library, rep27, enrichment PCR |
| GSM7110871 |
Differentiated HSPCs day 9 erythroid, GATA1 library, rep28, scRNA-seq |
| GSM7110872 |
Differentiated HSPCs day 9 erythroid, GATA1 library, rep28, enrichment PCR |
| GSM7110873 |
Differentiated HSPCs day 9 erythroid, GATA1 library, rep29, scRNA-seq |
| GSM7110874 |
Differentiated HSPCs day 9 erythroid, GATA1 library, rep29, enrichment PCR |
| GSM7110875 |
Differentiated HSPCs day 9 erythroid, GATA1 library, rep30, scRNA-seq |
| GSM7110876 |
Differentiated HSPCs day 9 erythroid, GATA1 library, rep30, enrichment PCR |
| GSM7110877 |
Differentiated HSPCs day 9 erythroid, GATA1 library, rep31, scRNA-seq |
| GSM7110878 |
Differentiated HSPCs day 9 erythroid, GATA1 library, rep31, enrichment PCR |
| GSM7110879 |
Differentiated HSPCs day 9 erythroid, GATA1 library, rep32, scRNA-seq |
| GSM7110880 |
Differentiated HSPCs day 9 erythroid, GATA1 library, rep32, enrichment PCR |
| GSM7110881 |
Bone marrow cells harvested from transplanted mice, CD33 mouse A, scRNA-seq and barcoded antibody (ADT) |
| GSM7110882 |
Bone marrow cells harvested from transplanted mice, CD33 mouse B, scRNA-seq and barcoded antibody (ADT) |
| GSM7110883 |
Bone marrow cells harvested from transplanted mice, NT mouse C, scRNA-seq and barcoded antibody (ADT) |
| GSM7110884 |
Bone marrow cells harvested from transplanted mice, NT mouse D, scRNA-seq and barcoded antibody (ADT) |
| GSM7110885 |
Differentiated HSPCs day 9 post-electroporation, donor 1, edited with c220_2T>C guide 1, replicate A, bulk RNA-seq |
| GSM7110886 |
Differentiated HSPCs day 9 post-electroporation, donor 1, edited with c220_2T>C guide 1, replicate B, bulk RNA-seq |
| GSM7110887 |
Differentiated HSPCs day 9 post-electroporation, donor 1, edited with c220_2T>C guide 1, replicate C, bulk RNA-seq |
| GSM7110888 |
Differentiated HSPCs day 9 post-electroporation, donor 2, edited with c220_2T>C guide 1, replicate A, bulk RNA-seq |
| GSM7110889 |
Differentiated HSPCs day 9 post-electroporation, donor 2, edited with c220_2T>C guide 1, replicate B, bulk RNA-seq |
| GSM7110890 |
Differentiated HSPCs day 9 post-electroporation, donor 2, edited with c220_2T>C guide 1, replicate C, bulk RNA-seq |
| GSM7110891 |
Differentiated HSPCs day 9 post-electroporation, donor 1, edited with c220_2T>C guide 2, replicate A, bulk RNA-seq |
| GSM7110892 |
Differentiated HSPCs day 9 post-electroporation, donor 1, edited with c220_2T>C guide 2, replicate B, bulk RNA-seq |
| GSM7110893 |
Differentiated HSPCs day 9 post-electroporation, donor 1, edited with c220_2T>C guide 2, replicate C, bulk RNA-seq |
| GSM7110894 |
Differentiated HSPCs day 9 post-electroporation, donor 2, edited with c220_2T>C guide 2, replicate A, bulk RNA-seq |
| GSM7110895 |
Differentiated HSPCs day 9 post-electroporation, donor 2, edited with c220_2T>C guide 2, replicate B, bulk RNA-seq |
| GSM7110896 |
Differentiated HSPCs day 9 post-electroporation, donor 2, edited with c220_2T>C guide 2, replicate C, bulk RNA-seq |
| GSM7110897 |
Differentiated HSPCs day 9 post-electroporation, donor 1, edited with c220_2T>C guide NT, replicate A, bulk RNA-seq |
| GSM7110898 |
Differentiated HSPCs day 9 post-electroporation, donor 1, edited with c220_2T>C guide NT, replicate B, bulk RNA-seq |
| GSM7110899 |
Differentiated HSPCs day 9 post-electroporation, donor 1, edited with c220_2T>C guide NT, replicate C, bulk RNA-seq |
| GSM7110900 |
Differentiated HSPCs day 9 post-electroporation, donor 2, edited with c220_2T>C guide NT, replicate A, bulk RNA-seq |
| GSM7110901 |
Differentiated HSPCs day 9 post-electroporation, donor 2, edited with c220_2T>C guide NT, replicate B, bulk RNA-seq |
| GSM7110902 |
Differentiated HSPCs day 9 post-electroporation, donor 2, edited with c220_2T>C guide NT, replicate C, bulk RNA-seq |
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| Relations |
| BioProject |
PRJNA889434 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE215253_RAW.tar |
44.2 Mb |
(http)(custom) |
TAR (of SF) |
| GSE215253_mouse_transplant_filtered_feature_bc_matrix.h5 |
18.6 Mb |
(ftp)(http) |
H5 |
| GSE215253_perturb_BE_seq_GATA1_rep10_filtered_feature_bc_matrix.h5 |
81.4 Mb |
(ftp)(http) |
H5 |
| GSE215253_perturb_BE_seq_GATA1_rep11_filtered_feature_bc_matrix.h5 |
94.5 Mb |
(ftp)(http) |
H5 |
| GSE215253_perturb_BE_seq_GATA1_rep12_filtered_feature_bc_matrix.h5 |
82.4 Mb |
(ftp)(http) |
H5 |
| GSE215253_perturb_BE_seq_GATA1_rep13_filtered_feature_bc_matrix.h5 |
83.0 Mb |
(ftp)(http) |
H5 |
| GSE215253_perturb_BE_seq_GATA1_rep14_filtered_feature_bc_matrix.h5 |
72.8 Mb |
(ftp)(http) |
H5 |
| GSE215253_perturb_BE_seq_GATA1_rep15_filtered_feature_bc_matrix.h5 |
71.5 Mb |
(ftp)(http) |
H5 |
| GSE215253_perturb_BE_seq_GATA1_rep17_filtered_feature_bc_matrix.h5 |
68.4 Mb |
(ftp)(http) |
H5 |
| GSE215253_perturb_BE_seq_GATA1_rep18_filtered_feature_bc_matrix.h5 |
67.6 Mb |
(ftp)(http) |
H5 |
| GSE215253_perturb_BE_seq_GATA1_rep19_filtered_feature_bc_matrix.h5 |
46.7 Mb |
(ftp)(http) |
H5 |
| GSE215253_perturb_BE_seq_GATA1_rep1_filtered_feature_bc_matrix.h5 |
81.9 Mb |
(ftp)(http) |
H5 |
| GSE215253_perturb_BE_seq_GATA1_rep20_filtered_feature_bc_matrix.h5 |
65.2 Mb |
(ftp)(http) |
H5 |
| GSE215253_perturb_BE_seq_GATA1_rep21_filtered_feature_bc_matrix.h5 |
58.7 Mb |
(ftp)(http) |
H5 |
| GSE215253_perturb_BE_seq_GATA1_rep22_filtered_feature_bc_matrix.h5 |
60.7 Mb |
(ftp)(http) |
H5 |
| GSE215253_perturb_BE_seq_GATA1_rep23_filtered_feature_bc_matrix.h5 |
57.7 Mb |
(ftp)(http) |
H5 |
| GSE215253_perturb_BE_seq_GATA1_rep24_filtered_feature_bc_matrix.h5 |
57.4 Mb |
(ftp)(http) |
H5 |
| GSE215253_perturb_BE_seq_GATA1_rep25_filtered_feature_bc_matrix.h5 |
35.3 Mb |
(ftp)(http) |
H5 |
| GSE215253_perturb_BE_seq_GATA1_rep27_filtered_feature_bc_matrix.h5 |
50.7 Mb |
(ftp)(http) |
H5 |
| GSE215253_perturb_BE_seq_GATA1_rep29_filtered_feature_bc_matrix.h5 |
36.5 Mb |
(ftp)(http) |
H5 |
| GSE215253_perturb_BE_seq_GATA1_rep2_filtered_feature_bc_matrix.h5 |
99.5 Mb |
(ftp)(http) |
H5 |
| GSE215253_perturb_BE_seq_GATA1_rep31_filtered_feature_bc_matrix.h5 |
39.1 Mb |
(ftp)(http) |
H5 |
| GSE215253_perturb_BE_seq_GATA1_rep32_filtered_feature_bc_matrix.h5 |
43.6 Mb |
(ftp)(http) |
H5 |
| GSE215253_perturb_BE_seq_GATA1_rep3_filtered_feature_bc_matrix.h5 |
73.9 Mb |
(ftp)(http) |
H5 |
| GSE215253_perturb_BE_seq_GATA1_rep4_filtered_feature_bc_matrix.h5 |
77.8 Mb |
(ftp)(http) |
H5 |
| GSE215253_perturb_BE_seq_GATA1_rep5_filtered_feature_bc_matrix.h5 |
83.4 Mb |
(ftp)(http) |
H5 |
| GSE215253_perturb_BE_seq_GATA1_rep6_filtered_feature_bc_matrix.h5 |
74.6 Mb |
(ftp)(http) |
H5 |
| GSE215253_perturb_BE_seq_GATA1_rep7_filtered_feature_bc_matrix.h5 |
74.8 Mb |
(ftp)(http) |
H5 |
| GSE215253_perturb_BE_seq_GATA1_rep8_filtered_feature_bc_matrix.h5 |
78.5 Mb |
(ftp)(http) |
H5 |
| GSE215253_perturb_BE_seq_GATA1_rep9_filtered_feature_bc_matrix.h5 |
80.2 Mb |
(ftp)(http) |
H5 |
| GSE215253_perturb_BE_seq_HbF_rep1_filtered_feature_bc_matrix.h5 |
18.9 Mb |
(ftp)(http) |
H5 |
| GSE215253_perturb_BE_seq_HbF_rep2_filtered_feature_bc_matrix.h5 |
11.0 Mb |
(ftp)(http) |
H5 |
| GSE215253_perturb_BE_seq_HbF_rep3_filtered_feature_bc_matrix.h5 |
10.7 Mb |
(ftp)(http) |
H5 |
| GSE215253_perturb_BE_seq_HbF_rep4_filtered_feature_bc_matrix.h5 |
9.0 Mb |
(ftp)(http) |
H5 |
| GSE215253_perturb_BE_seq_HbF_rep5_filtered_feature_bc_matrix.h5 |
15.2 Mb |
(ftp)(http) |
H5 |
| GSE215253_perturb_BE_seq_HbF_rep6_filtered_feature_bc_matrix.h5 |
14.5 Mb |
(ftp)(http) |
H5 |
| GSE215253_perturb_BE_seq_HbF_rep7_filtered_feature_bc_matrix.h5 |
16.0 Mb |
(ftp)(http) |
H5 |
| GSE215253_perturb_BE_seq_HbF_rep8_filtered_feature_bc_matrix.h5 |
19.5 Mb |
(ftp)(http) |
H5 |
| GSE215253_perturb_seq_CD33_gex_rep1_filtered_feature_bc_matrix.h5 |
29.2 Mb |
(ftp)(http) |
H5 |
| GSE215253_perturb_seq_CD33_gex_rep2_filtered_feature_bc_matrix.h5 |
27.1 Mb |
(ftp)(http) |
H5 |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
| Processed data provided as supplementary file |
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