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Series GSE89020 Query DataSets for GSE89020
Status Public on Oct 01, 2018
Title Parallel transcriptional programs driving early-starting inheritable lineage bias of myeloid, lymphoid and dendritic cells are initiated by distinct dosage of PU.1 and IRF8 in HSCs
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Summary In the traditional model of hematopoiesis, blood lineages diversify from HSCs through a sequential process of hierarchical bifurcation. Each of these bifurcation nodes comprises multipotent progenitors that are assumed to be homogeneous and equipotent in terms of their potency. The isolation of dendritic cell (DC) progenitors with either myeloid or lymphoid potency has led to the notion of “convergent development”, and an ongoing debate on the origin of DCs and their relationship with myeloid and lymphoid lineages. We have used a clonal assay combining with statistical modeling to quantify the yield of granulocytes (G), monocytes (M), lymphocytes (L) and three subsets of DCs from single human CD34+ progenitor cells of nine different phenotypes, and traced the potency of their individual progeny. We show that multipotent progenitors are not in fact equipotent, but instead exhibit a bias toward one specific lineage; this lineage bias is established at the HSC stage and transmitted to most progeny, with bifurcation to other lineages only occurring infrequently. Critically, these lineage biases can be correlated to lineage-specific transcriptional programs that are reinforced during division. We performed computational analysis to correlate transcriptomes and lineage composition of individual phenotype-defined progenitor cells. This enabled us to identify 32 common transcription factor (TF) candidates that interact physically and form genetic regulatory networks, with lineage-specific developmental programs initiated and reinforced based on the distinct dosage combination of these common TFs. Our analysis reveals that early expression of high levels of IRF8 and intermediate levels of PU.1 protein correlates with a bias towards CD141+ DC and plasmacytoid DC lineages in vivo, and that this pattern is inheritable from progenitors to mature cells. We have therefore arrived at a coherent model of DC development driven by parallel and inheritable programs defined by distinct dosages of TFs including PU.1 and IRF8, a developmental model that may apply to other lineages as well.
Overall design mRNA profiles of human cord blood CD34+ hematopoietic progenitors from healthy donors
Contributor(s) Liu K, Zhou YJ, Ma W, Shen Y
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Submission date Oct 21, 2016
Last update date May 15, 2019
Contact name Kang Liu
Phone 212-305-0839
Organization name Columbia University
Department Dept of Microbiology & Immunology
Lab Liu Lab
Street address 701 W. 168 St., HHSC 1208
City New York City
State/province New York
ZIP/Postal code 10032
Country USA
Platforms (1)
GPL18573 Illumina NextSeq 500 (Homo sapiens)
Samples (26)
GSM2357501 MDP [KY003]
GSM2357502 CMP [KY005]
GSM2357503 GMDP [KY006]
BioProject PRJNA349810
SRA SRP091908

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Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE89020_cord_blood_progenitor_bulk_data.txt.gz 944.5 Kb (ftp)(http) TXT
GSE89020_cord_blood_progenitor_bulk_data_normalized.txt.gz 2.1 Mb (ftp)(http) TXT
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Processed data are available on Series record
Raw data are available in SRA

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