Early innate lymphoid progenitors (EILP) have recently been identified in the mouse adult bone marrow as a multipotential progenitor population committed to ILC lineages, but their relationship with other described ILC progenitors is still unclear. In this study, we examine the progenitor-successor relationships between EILP, IL-7R+ common lymphoid progenitors (ALP), and ILC precursors (ILCp). Bioinformatic, phenotypical, functional, and genetic approaches collectively establish EILP as an intermediate progenitor between ALP and ILCp. Our work additionally provides new candidate regulators of ILC development and clearly defines the stage of requirement of transcription factors key for early ILC development. Overall design: transcriptional profiling of early ILC progenitors (EILP, ILCp), and common lymphoid progenitors (ALP) was performed by RNA sequencing
Development and differentiation of early innate lymphoid progenitors.
Specimen part, Cell line, SubjectView Samples
Gene expression profiling was performed to identify INSL4-regulated gene program in non-small cell lung cancer A549 cells. We compared gene expression profiles of A549 cells transduced with lentiviruses expressing scrambled shRNA control or INSL4 shRNA. Our analysis revealed INSL4-regulated gene program that are involved in the regulation of cell cycle, growth and survival.
Role of INSL4 Signaling in Sustaining the Growth and Viability of LKB1-Inactivated Lung Cancer.
Cell lineView Samples
Gene expression profiling was performed on control and long intergenic non-protein coding RNA 473 (LINC00473)-depleted human mucoepidermoid carcinoma H3118 cells, and differentially expressed genes after LINC00473 depletion were identified.
CRTC1-MAML2 fusion-induced lncRNA LINC00473 expression maintains the growth and survival of human mucoepidermoid carcinoma cells.
Specimen part, Cell lineView Samples
ILC210 represent a distinct effector population of ILC2 cells that have regulatory potential Overall design: comparison between ILC2 cells with IL-33 stimulation or not on transcriptome change
Alternative activation generates IL-10 producing type 2 innate lymphoid cells.
Specimen part, SubjectView Samples
Subtypes of innate lymphoid cells (ILC), defined by effector function and transcription factor expression, have recently been identified. In the adult, ILC derive from common lymphoid progenitors in bone marrow, although transcriptional regulation of the developmental pathways involved remains poorly defined. TOX is required for development of lymphoid tissue inducer cells, a type of ILC3 required for lymph node organogenesis, and NK cells, a type of ILC1. We show here that production of multiple ILC lineages requires TOX, as a result of TOX-dependent development of common ILC progenitors. Comparative transcriptome analysis demonstrated failure to induce various aspects of the ILC gene program in the absence of TOX, implicating this nuclear factor as a key early determinant of ILC lineage specification. Overall design: TOX KO vs. wild tyype
The development of innate lymphoid cells requires TOX-dependent generation of a common innate lymphoid cell progenitor.
No sample metadata fieldsView Samples
To understand the temporal changes occurring in adipose tissue gene expression during a one-year weightloss intervention, adipose tissue biopsies were collected from 19 healthy obese individuals at three time points.
Subcutaneous adipose tissue gene expression and DNA methylation respond to both short- and long-term weight loss.
Sex, Specimen part, TimeView Samples
Genetically engineered mice developed spontaneous pancreas cancer (Pdx-Cre;LSL-KRASG12D;P53Mut). Mice were also engineered to develop similar spontaneous pancreas cancer without Twist or Snail (conditional gene knockout). The pancreas tumors were harvested and analysed for gene expression profiles comparisons.
Epithelial-to-mesenchymal transition is dispensable for metastasis but induces chemoresistance in pancreatic cancer.
Specimen partView Samples
Mucoepidermoid carcinomas (MEC) is the most common salivary gland malignancy. To date, advanced and nonresectable MEC have poor prognosis and no effective treatment. The CRTC1-MAML2 fusion oncogene, which is associated with more than 50% of MEC, consists of the N-terminal CREB-binding domain of the CREB transcriptional co-activator CRTC1 and the C-terminal transcriptional activation domain of the Notch transcriptional co-activator MAML2. CRTC1-MAML2 fusion was found to interact with CREB and constitutively activate their transcriptional targets. To investigate the genes and pathways regulated by CRTC1-MAML2 fusion oncogene, gene expression profiling analysis were performed in human fusion-positive MEC cells before and after knockdown of both CRTC1-MAML2 and MAML2 as well as in human fusion-negative salivary gland cancer cells before and after MAML2 knockdown only. This study revealed specific transcriptional program induced by the CRTC1-MAML2 fusion oncogene, which potentially mediates CRC1-MAML2 functions in MEC initiation and maintenance. The information will be useful for developing new approaches to block CRTC1-MAML2 fusion-expressing MEC.
Aberrantly activated AREG-EGFR signaling is required for the growth and survival of CRTC1-MAML2 fusion-positive mucoepidermoid carcinoma cells.
Cell lineView Samples
To assess how the TOX3 nuclear protein can modulate gene expression in luminal epithelial cells, MCF7 cells were transfected with a TOX3 expression vector or vector control. In both instances, GFP was coexpressed, allowing isolation of transfected cells by flow cytometry before transcriptome analysis. Experiments were carried out under estrogen depleted conditions, and cells isolated 48 hours after transfection.
TOX3 is expressed in mammary ER(+) epithelial cells and regulates ER target genes in luminal breast cancer.
Cell lineView Samples