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SRP158666
Mus musculus
2756 Downloadable Samples
Illumina HiSeq 2500
Description
During cortical development, distinct subtypes of glutamatergic neurons are sequentially born and differentiate from dynamic populations of progenitors. How progenitors and their daughter cells are temporally patterned remains unknown. Here, we trace the transcriptional trajectories of successive generations of apical progenitors (APs) and isochronic cohorts of their daughter neurons in the developing mouse neocortex using high temporal resolution parallel single-cell RNA sequencing. We identify and functionally characterize a core set of evolutionarily-conserved temporally patterned genes which drive APs from internally-driven states to more exteroceptive states, revealing a progressively increasing role for extracellular signals as corticogenesis unfolds. These embryonic age-dependent AP molecular states are reflected in their neuronal progeny as successive ground states, onto which essentially conserved early post-mitotic differentiation programs are applied. Thus, temporally unfolding molecular birthmarks present in progenitors act in their post-mitotic progeny as seeds for adult neuronal diversity. Overall design: Investigation of the transcriptional dynamics in time-locked cohorts of cortical cells across embryonic neurogenesis. Flashtag is injected at 4 ages (E12, E13, E14, E15), and cells collected 1H, 24H, 96H after birth (= a total of 12 conditions) and analyzed by single cell transcriptomics.
Publication Title
Temporal patterning of apical progenitors and their daughter neurons in the developing neocortex.
Sample Metadata Fields
Subject
View Samples- Mus musculus
- 4 Downloadable Samples
- Illumina HiSeq 2500
Description
Sensory functions of the vagus nerve are critical for specific aware perceptions and for monitoring visceral functions in the cardio-pulmonary and gastrointestinal systems. Here we present a comprehensive identification, classification, and validation of the neuron types in the neural crest (jugular) and placode (nodose) derived vagal ganglia by single cell transcriptomic (scRNA-seq) analysis. Our results reveal major differences between neurons derived from different embryonic origins. Jugular neurons exhibit fundamental similarities to the somatosensory spinal neurons, including major types such as C-low threshold mechanoreceptors (C-LTMRs), A-LTMRs, Ad-nociceptors, cold-, and mechano-heat C-nociceptors. In contrast, the nodose ganglion contains 18 distinct types dedicated to surveying the physiological state of the internal body. Our results reveal a vast diversity of vagal neuron types including many previously unanticipated types as well as proposed types that are consistent with chemoreceptors, nutrient detectors, baroreceptors, and stretch and volume mechanoreceptors of the respiratory, gastrointestinal, and cardiovascular systems. Overall design: Single-cell RNA-seq from 1896 vagal ganglion cells derived from wild-type and Vglut2Cre-Tomato animals originating from four replicates and consisting of the neuronal and non-neuronal cells that make up the ganglionic tissue.
Publication Title
An Atlas of Vagal Sensory Neurons and Their Molecular Specialization.
Sample Metadata Fields
Age, Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 9 Downloadable Samples
Affymetrix Human Gene 1.1 ST Array (hugene11st)
Description
Lineage specific transcription factors (TF) define and reinforce tissue specific cell types. For instance, stable endoderm progenitors were established from human ESC by constitutive expression of SOX7 or SOX17. We hypothesized that combinatorial expression of OCT4, SOX2 and KLF4together with the neural-lineage TF, Zic3, could directly convert fibroblasts into stable neuronal progenitor cells (NPC). Ensuing colonies predominantly expressed genes present in human NPC, as demonstrated by genome wide transcriptional analysis, and this phenotype could be maintained through many passages. When injected in immunodeficient mice, Zic3-induced (Zi)NPC form neuroendocrine tumors without evidence of mesoderm or endoderm. In vitro, ZiNPC spontaneously differentiated to neural cells only, and could be differentiated into astrocytes, oligodendrocytes and motor neuron lineages. In conclusion, addition of Zic3 during induced pluripotent stem cell (iPSC) generation, allows for the derivation of stable neural lineage progenitor cells.
Publication Title
Zic3 induces conversion of human fibroblasts to stable neural progenitor-like cells.
Sample Metadata Fields
Sex, Specimen part, Disease, Cell line, Treatment
View Samples- Homo sapiens
- 4 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This study sought to provide a novel ex vivo model for analyzing healing kinetics and gene expression of primary human gingival fibroblasts (hGF) within collagen scaffolds.
Publication Title
Cell population kinetics of collagen scaffolds in ex vivo oral wound repair.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 14 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The specific ablation of Rb1 gene in stratified epithelia (RbF/F;K14cre) promotes proliferation and altered differentiation but is insufficient to produce spontaneous tumors. The pRb relative, p107, compensates some of the functions of pRb in these tissues, however RbF/F;K14cre;p107-/- mice die postnatally. Acute pRb loss in stratified epithelia, using an inducible mouse model (RbF/F;K14creERTM), shows that p107 exerts specific tumor suppressor functions in its absence. After simultaneous absence of pRb and p107, p53 transcriptional function is impaired and Pten expression is reduced. All mutant mice develop spontaneous squamous tumors carcinomas rapidly. Gene expression analysis of mouse tumors, besides supporting the impaired p53 function and the susceptibility to Akt/mTOR inhibitors, also revealed significant overlap with human squamous carcinomas. Thus, RbF/F;K14creERTM;p107-/- may constitute a new mouse model for these malignancies. Collectively, these data demonstrate the existence of a previously unreported functional connection between pRb, Pten and p53 tumor suppressors, through p107, of a particular relevance in squamous tumor development.
Publication Title
A novel tumor suppressor network in squamous malignancies.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 38 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Endothelial cells (EC) lining arteries and veins have distinct molecular and functional signatures. The (epi)genetic regulatory mechanisms underlying this heterogeneity in human EC are incompletely understood. Using genome-wide microarray screening we established a specific fingerprint of freshly isolated arterial (HUAEC) and venous EC (HUVEC) from human umbilical cord comprising 64 arterial and 12 venous genes, representing distinct functions and pathways. Among the arterial genes were 8 transcription factors, including HEY2, a downstream target of Notch signaling and the current golden standard pathway for arterial EC specification. Short-term culture of HUAEC or HUVEC abrogated differential gene expression resulting in a default state. Erasure of arterial gene expression was at least in part due to loss of canonical Notch activity and HEY2 expression. Notably, nCounter analysis revealed that restoring HEY2 expression or Delta-like 4 (Dll4)-induced Notch signaling in cultured HUVEC or HUAEC only partially reinstated the arterial EC gene signature while combined overexpression of the 8 transcription factors restored this fingerprint much more robustly. Each transcription factor had a different impact on gene regulation, with some stimulating only few and others boosting a large proportion of arterial genes. Interestingly, although there was some overlap and cross-regulation, the transcription factors largely complemented each other in regulating the arterial EC gene profile. Thus, our study showed that Notch signaling determines only part of the arterial EC signature and identified additional novel and complementary transcriptional players in the complex regulation of human arteriovenous EC identity
Publication Title
Unraveling a novel transcription factor code determining the human arterial-specific endothelial cell signature.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 4 Downloadable Samples
- Affymetrix Human Gene 2.0 ST Array (hugene20st)
Description
The combination of defined factors with small molecules targeting epigenetic factors is a strategy that has been shown to enhance optimal derivation of human iPSCs and could be used for therapeutic and regenerative medicine applications. In this study, we showed that a new first-in-class dual G9a/DNMT inhibitor CM272 compound improves the standard four-factor reprogramming efficiency of human fibroblast. The use of CM272 facilitates the generation of iPSC with only two factors, OCT4 and SOX2, allowing the removal of potentially oncogenic factors such as cMYC or KLF4. Taking a closer look at the early events occurring during cell reprogramming we demonstrated that treatment with our G9a/DNMT dual inhibitor induces heterochromatin relaxation, facilitates the engagement of OCT4 and SOX2 transcription factors to the genome and promotes mesenchymal to epithelial transition during cell reprogramming. Thus, the use of this new G9a/DNMT dual inhibitor compound may represent an interesting alternative for improving cell reprogramming.
Publication Title
Reversible dual inhibitor against G9a and DNMT1 improves human iPSC derivation enhancing MET and facilitating transcription factor engagement to the genome.
Sample Metadata Fields
Sex, Specimen part, Disease, Cell line
View Samples- Mus musculus
- 16 Downloadable Samples
- Illumina HiSeq 4000
Description
Gata2, a zinc finger TF, is essential for the generation and survival of HSCs in the embryo and has been implicated in the pathogenesis of AML, yet the requirement for Gata2 in adult HSCs and LSCs remains unclear. Using a conditional mouse model where Gata2 was deleted specifically in hematopoietic cells, we show that knockout of Gata2 leads to a rapid and complete cell-autonomous loss of adult HSCs. In Meis1a/Hoxa9 driven AML, deletion of Gata2 impedes maintenance and self-renewal of LSCs. We then performed RNA-seq from sorted control and Gata2 KO LSCs (CD45.2+ c-Kit+) after pIpC treatment in transplanted mice. Overall design: Wild Type and Gata2-/- Meis1a/Hoxa9 LSCs were harvested from mice 24 days after pIpC administration
Publication Title
Gata2 as a Crucial Regulator of Stem Cells in Adult Hematopoiesis and Acute Myeloid Leukemia.
Sample Metadata Fields
Cell line, Subject
View Samples- Mus musculus
- 8 Downloadable Samples
- Illumina HiSeq 4000
Description
Gata2, a zinc finger TF, is essential for the generation and survival of HSCs in the embryo and has been implicated in the pathogenesis of AML, yet the requirement for Gata2 in adult HSCs and LSCs remains unclear. Using a conditional mouse model where Gata2 was deleted specifically in hematopoietic cells, we show that knockout of Gata2 leads to a rapid and complete cell-autonomous loss of adult HSCs. We then performed RNA-seq in sorted HSCs (LSK CD48- CD150+) from control and Gata2+/fl;Vav-iCre+ 8-to-10-week old mice. Overall design: Wild Type and Gata2+/- HSCs were harvested from 8-to-10-week old mice
Publication Title
Gata2 as a Crucial Regulator of Stem Cells in Adult Hematopoiesis and Acute Myeloid Leukemia.
Sample Metadata Fields
Cell line, Subject
View Samples- Homo sapiens
- 9 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
High-throughput sequencing analysis of the chromosome 7q32 deletion reveals IRF5 as a potential tumour suppressor in splenic marginal-zone lymphoma.
Sample Metadata Fields
Specimen part, Disease, Disease stage
View Samples