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SRP075476
Mus musculus
158 Downloadable Samples
Illumina HiSeq 2500
Description
Tissue resident macrophages are functionally diverse cells that share an embryonic mesodermal origin. However, the mechanism(s) that control their specification remain unclear. We performed transcriptional, molecular and in situ spatio-temporal analyses of macrophage development in mice. We report that Erythro-Myeloid Progenitors generate pre-macrophages (pMacs) that simultaneously colonize the head and caudal embryo from embryonic day (E)9.5 in a chemokine-receptor dependent manner, to further differentiate into tissue F4/80+ macrophages. The core macrophage transcriptional program initiated in pMacs, is rapidly diversified in early macrophages as expression of transcriptional regulators becomes tissue-specific. For example, the preferential expression of the transcriptional regulator Id3 initiated in early fetal liver macrophages appears critical for Kupffer cell differentiation, as inactivation of Id3 causes a selective Kupffer cell deficiency that persists in adults. We propose that colonization of developing tissues by differentiating macrophages is immediately followed by their specification as they establish residence, hereby generating the macrophage diversity observed in post-natal tissues. Overall design: RNA-sequencing of sorted macrophage cell populations (Mac) and progenitors (EMP, pMac) from various tissues and collected at different time points, including technical and biological replicates
Publication Title
Specification of tissue-resident macrophages during organogenesis.
Sample Metadata Fields
Specimen part, Subject, Time
View Samples- Mus musculus
- 1 Downloadable Sample
- Illumina HiSeq 1500
Description
Tissue resident macrophages are functionally diverse cells that share an embryonic mesodermal origin. However, the mechanism(s) that control their specification remain unclear. We performed transcriptional, molecular and in situ spatio-temporal analyses of macrophage development in mice. We report that Erythro-Myeloid Progenitors generate pre-macrophages (pMacs) that simultaneously colonize the head and caudal embryo from embryonic day (E)9.5 in a chemokine-receptor dependent manner, to further differentiate into tissue F4/80+ macrophages. The core macrophage transcriptional program initiated in pMacs, is rapidly diversified in early macrophages as expression of transcriptional regulators becomes tissue-specific. For example, the preferential expression of the transcriptional regulator Id3 initiated in early fetal liver macrophages appears critical for Kupffer cell differentiation, as inactivation of Id3 causes a selective Kupffer cell deficiency that persists in adults. We propose that colonization of developing tissues by differentiating macrophages is immediately followed by their specification as they establish residence, hereby generating the macrophage diversity observed in post-natal tissues. Overall design: RNA-sequencing of sorted macrophage cell populations (Mac) and progenitors (EMP, pMac) from various tissues and collected at different time points, including technical and biological replicates
Publication Title
Specification of tissue-resident macrophages during organogenesis.
Sample Metadata Fields
Specimen part, Subject, Time
View Samples- Homo sapiens
- 9 Downloadable Samples
- IlluminaHiSeq1500
Description
Direct conversion of somatic cells into neural stem cells (NSCs) by defined factors holds great promise for mechanistic studies, drug screening, and potential cell therapies for different neurodegenerative diseases. Here, we report that a single zinc-finger transcription factor, Zfp521, is sufficient for direct conversion of human fibroblasts into long-term self-renewable and multipotent NSCs. In vitro, Zfp521-induced NSCs maintained their characteristics in the absence of exogenous factor expression and exhibited morphological, molecular, developmental, and functional properties that were similar to control NSCs. Additionally, the single seeded induced NSCs were able to form NSC colonies with efficiency comparable to control NSCs and expressed NSC markers. The converted cells were capable of surviving, migrating and attaining neural phenotypes after transplantation into neonatal mouse- and adult rat brains, without forming tumors. Moreover, the Zfp521-induced NSCs predominantly expressed rostral genes. Our results suggest a facilitated approach for establishing human NSCs through Zfp521-driven conversion of fibroblasts. Overall design: RNA-Seq of 3 replicates each of iNSC, WT-NSC, and HNF
Publication Title
Conversion of Human Fibroblasts to Stably Self-Renewing Neural Stem Cells with a Single Zinc-Finger Transcription Factor.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 93 Downloadable Samples
- Illumina HiSeq 2000
Description
Dendritic cells (DC) are professional antigen-presenting cells that orchestrate immune responses. The human DC population comprises two main functionally-specialized lineages, whose origins and differentiation pathways remain incompletely defined. Here we combine two high-dimensional technologies — single-cell mRNA sequencing and Cytometry by Time-of-Flight (CyTOF), to identify human blood CD123+CD33+CD45RA+ DC precursors (pre-DC). Pre-DC share surface markers with plasmacytoid DC (pDC) but have distinct functional properties that were previously attributed to pDC. Tracing the differentiation of DC from the bone marrow to the peripheral blood revealed that the pre-DC compartment contains distinct lineage-committed sub-populations including one early uncommitted CD123high pre-DC subset and two CD45RA+CD123low lineage-committed subsets exhibiting functional differences. The discovery of multiple committed pre-DC populations opens promising new avenues for the therapeutic exploitation of DC subset-specific targeting. Overall design: Single cell mRNA sequencing was used to investigate the transcriptomic relationships within the dendritic cell precursors within the peripheral blood.
Publication Title
Mapping the human DC lineage through the integration of high-dimensional techniques.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 51 Downloadable Samples
Illumina HumanHT-12 V3.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Cellular Differentiation of Human Monocytes Is Regulated by Time-Dependent Interleukin-4 Signaling and the Transcriptional Regulator NCOR2.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 51 Downloadable Samples
- Illumina HumanHT-12 V3.0 expression beadchip
Description
Whole transcriptome profiling (Illumina Microarray) of human ex vivo lymphocytes and monocytes, as well as of human monocyte-derived cells generated in vitro by activating CD14+ monocytes with MCSF, GMCSF or the combination of GMCSF and IL4
Publication Title
Cellular Differentiation of Human Monocytes Is Regulated by Time-Dependent Interleukin-4 Signaling and the Transcriptional Regulator NCOR2.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 20 Downloadable Samples
- Illumina HiSeq 1500
Description
Whole transcriptome profiling (RNA-Seq) of a time kinetics experiment containing human monocyte-derived cells, which were activated with IL4 either directly at the start of the culture, or at different hours after an initial activation with GMCSF alone. Cells being activated solely with GMCSF were added as controls Overall design: CD14+ monocytes were FACS-sorted from blood of human healthy donors and later activated in vitro with either GMCSF alone for 72 hours to obtain Mo-GMCSF[IL4 (0h)] cells as controls, with the combination of GMCSF and IL4 for 72 hours or 144 hours to obtain Mo-GMCSF[IL4 (0-72h)] or Mo-GMCSF[IL4 (0-144h)] cells, respectively, or with first GMCSF and then with the combination of GMCSF and IL4 for different durations. For the latter, monocytes were first activated with GMCSF for either 12, 24, 48 or 72 hours, and then with GMCSF plus IL4 until a total activation time of 144 hours. This resulted in Mo-GMCSF[IL4 (12-144h)], Mo-GMCSF[IL4 (24-144h)] , Mo-GMCSF[IL4 (48-144h)] and Mo-GMCSF[IL4 (72-144h)] cells, respectively.
Publication Title
Cellular Differentiation of Human Monocytes Is Regulated by Time-Dependent Interleukin-4 Signaling and the Transcriptional Regulator NCOR2.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 6 Downloadable Samples
- Illumina HiSeq 1500
Description
Whole transcriptome profiling (RNA-Seq) was performed on human Mo-GMCSF[IL4 (0-72h)] cells with either NCOR2 being knocked down or corresponding WT cells Overall design: CD14+ monocytes were FACS-sorted from blood of human healthy donors and later activated in vitro with the combination of GMCSF and IL4 for 72h to obtain Mo-GMCSF[IL4 (0-72h)] cells. During the last 24 hours of activation, either siRNAs targeting NCOR2 or scrambled RNAs were added to obtain NCOR2 knock down cells and corresponding WT cells, respectively
Publication Title
Cellular Differentiation of Human Monocytes Is Regulated by Time-Dependent Interleukin-4 Signaling and the Transcriptional Regulator NCOR2.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 2 Downloadable Samples
- Illumina HiSeq 1500
Description
Dendritic cells (DC) are professional antigen-presenting cells that orchestrate immune responses. The human DC population comprises two main functionally-specialized lineages, whose origins and differentiation pathways remain incompletely defined. Here we combine two high-dimensional technologies — single-cell mRNA sequencing and Cytometry by Time-of-Flight (CyTOF), to identify human blood CD123+CD33+CD45RA+ DC precursors (pre-DC). Pre-DC share surface markers with plasmacytoid DC (pDC) but have distinct functional properties that were previously attributed to pDC. Tracing the differentiation of DC from the bone marrow to the peripheral blood revealed that the pre-DC compartment contains distinct lineage-committed sub-populations including one early uncommitted CD123high pre-DC subset and two CD45RA+CD123low lineage-committed subsets exhibiting functional differences. The discovery of multiple committed pre-DC populations opens promising new avenues for the therapeutic exploitation of DC subset-specific targeting. Overall design: single-cell RNA Seq of human dendritic cells
Publication Title
Mapping the human DC lineage through the integration of high-dimensional techniques.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 8 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Atopic dermatitis, a chronic inflammatory skin disease with increasing prevalance, is closely associated with skin barrier defects. A cytokine related to disease severity and inhibition of keratinocyte differentiation is IL-31. To identify its molecular targets, IL-31-dependent gene expression was determined in 3-dimensional organotypic skin models.
Publication Title
Control of the Physical and Antimicrobial Skin Barrier by an IL-31-IL-1 Signaling Network.
Sample Metadata Fields
Sex, Specimen part
View Samples