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Status |
Public on Jul 01, 2020 |
Title |
Clonal multi-omics in DC development |
Organism |
Mus musculus |
Experiment type |
Expression profiling by high throughput sequencing
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Summary |
Despite major developments in single cell multi-omics approaches, a single stem or progenitor cell can only be tested once. Here we develop ‘clonal multi-omics’, where recent daughters of a clone act as surrogates of the parental cell allowing multiple tests of its molecular profile and/or cellular fate under different conditions. We first present SIS-seq – a novel clonal method whereby siblings are examined in parallel for gene expression by RNA-seq, or for fate after culture. We use this method to identify, then validate using CRISPR, the genes expressed in single haematopoietic progenitors that control the development of the different dendritic cell (DC) subtypes. In this way, Bcor is identified as a suppressor of plasmacytoid DC (pDC) and conventional DC subtype 2 (cDC2) numbers during Flt3 ligand-mediated ‘emergency’ DC development. Using a complementary method SIS-skew – where WT and BcorKO siblings of the same clone are examined in parallel for fate – we discover that Bcor restricts clonal expansion, especially for generation of cDC2s, and suppresses clonal fate potential, especially for pDCs. SIS-seq and SIS-skew therefore represent novel and broadly applicable clonal multiomics approaches that can reveal the molecular and cellular mechanisms governing cell function at a single cell level, including after genetic or extrinsic factor perturbation.
This SuperSeries is composed of the SubSeries listed below.
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Overall design |
Refer to individual Series
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Citation missing |
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Submission date |
Jul 01, 2020 |
Last update date |
Jul 16, 2020 |
Contact name |
Luyi Tian |
E-mail(s) |
ltian@broadinstitute.org
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Phone |
8577779729
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Organization name |
Broad institute
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Lab |
Fei Chen Lab
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Street address |
415 main st Cambridge
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City |
Cambridge |
State/province |
MA |
ZIP/Postal code |
02142 |
Country |
USA |
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Platforms (2) |
GPL16417 |
Illumina MiSeq (Mus musculus) |
GPL19057 |
Illumina NextSeq 500 (Mus musculus) |
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Samples (164)
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This SuperSeries is composed of the following SubSeries: |
GSE119097 |
SIS-seq, a molecular ‘time machine’, connects single cell fate with gene programs |
GSE153675 |
Clonal multi-omics reveals Bcor as a regulator of dendritic cell development and its action at a clonal level |
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Relations |
BioProject |
PRJNA643625 |