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Series GSE124875 Query DataSets for GSE124875
Status Public on Jan 10, 2020
Title Notch ligand Dll4 impairs the recruitment of hemogenic cells into intra-aortic clusters and limits hematopoietic stem cell production.
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary Hematopoietic stem cells (HSCs) develop from the hemogenic endothelium in the embryonic aorta. In most vertebrates, hemogenic cells protrude into the aortic lumen forming clusters where the hematopoietic features are acquired. Although much is known about the molecular characteristics of the hematopoietic cells, we still lack basic understanding on the origin and 3D-organization of intraortic hematopoietic clusters (IAHC) in the mouse embryo and how they evolve over time. Here we use advanced live imaging techniques of organotypic slice cultures, clonal analysis, and mathematical modelling to show that IAHC formation is a two-step process. First, a hemogenic progenitor buds up from the endothelium and undergoes division forming the monoclonal core of the cluster. Next, cells from the surrounding hemogenic endothelium are recruited into the IAHCs, increasing their size and heterogeneity. We found that the recruitment phase of IAHC formation is negatively regulated by Notch signalling via the Delta-like-4 (Dll4) Notch ligand. We show that blocking of Dll4 promotes the entrance of new hemogenic Gfi1+ cells into the IAHC and increases the number of cells that acquire HSC activity. Mathematical modelling based on our data provides estimation of the cluster lifetime and the average recruitment time of hemogenic cells to the cluster under physiologic and Dll4-inhibited conditions. Single cell transcriptomic analysis indicates that cell identities are preserved after Dll4 blockage. Our data provides for the first time a detailed characterization of the aortic hematopoietic stem cell niche and its maturation dynamics, identifying the Notch ligand Dll4 as a major molecular player governing dynamics of cluster formation and HSCs production.
Overall design Detection of differentially expressed genes in three cell populations, treated or not with DII4 antibody
Contributor(s) Bigas A, Porcheri C, Ruiz-Herguido C, Guillén Y
Citation(s) 32149421
Submission date Jan 09, 2019
Last update date Apr 17, 2020
Contact name Anna Bigas
Phone +34933160440
Organization name Institut Hospital del Mar d'Investigacions Mèdiques
Department Cancer Research
Lab Stem Cells and Cancer
Street address Dr. Aiguader 88
City Barcelona
State/province Barcelona
ZIP/Postal code 08003
Country Spain
Platforms (1)
GPL13112 Illumina HiSeq 2000 (Mus musculus)
Samples (24)
GSM3557761 CD31p_ckitp_CD45m_Control1
GSM3557762 CD31p_Ckitm_CD41p_CD45m_Control1
GSM3557763 CD31p_ckitp_CD45p_Control1
BioProject PRJNA514056
SRA SRP178201

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Supplementary file Size Download File type/resource
GSE124875_normalized_log2_htseq_counts_annot.txt.gz 3.6 Mb (ftp)(http) TXT
GSE124875_raw_htseq_counts.txt.gz 862.5 Kb (ftp)(http) TXT
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Raw data are available in SRA
Processed data are available on Series record

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