Biology subjects

Yeung, K.

Publications and source records attributed to Yeung, K..

4 recordsLinked to original sources

bioRxiv2023

Integrative Genomic Analyses Reveal Putative Cell Type-specific Targets of the Drosophila Ets Transcription Factor Pointed

The Ets domain transcription factors direct diverse biological processes throughout all metazoans and are implicated in development as well as in tumor initiation, progression and metastasis. The Drosophila Ets transcription factor Pointed (Pnt) is required for several aspects of eye development and regulates cell cycle progression, specification, and differentiation. Despite its critical role in development, very few targets of Pnt have been reported previously. Here, we used chromatin immunoprecipitation with high-throughput sequencing (ChIP-seq) to determine the genome-wide occupancy of Pnt in late larval eye discs. We identified enriched regions that mapped to an average of 6,941 genes, the vast majority of which are novel putative Pnt targets. Integrating ChIP-seq data with two other larval eye single cell genomics datasets (scRNA-seq and snATAC-seq) reveals genes that may be putative cell type-specific genes regulated by Pnt. Finally, our ChIP-seq data predict cell type-specific functional enhancers that were not reported previously. Our study provides a greatly expanded list of putative Pnt targets in the eye and is a resource for future studies that will allow mechanistic insights into complex developmental processes regulated by Pnt.

genomics↗

bioRxiv2023

A Single Cell Genomics Atlas of the Drosophila Larval Eye Reveals Distinct Developmental Timelines and Novel Markers for All Photoreceptor Subtypes

The Drosophila eye is a powerful model system to study principles of cell differentiation, proliferation, survival and morphogenesis. However, a high-resolution single cell genomics resource that accurately captures all major cell types of the larval eye disc and their spatiotemporal relationships is lacking. Here, we report transcriptomic and chromatin accessibility data for all known cell types in the developing eye. Photoreceptors appear as streams of cells that represent dynamic developmental timelines. Photoreceptor subtypes are transcriptionally distinct when they begin to differentiate, but then converge upon a common transcriptome just 24 hours later. We identify novel cell type-specific marker genes, enhancers and potential regulators, as well as genes with distinct R3 or R4 photoreceptor specific expression. Finally, we observe that photoreceptor chromatin accessibility is more permissive than non-neuronal lens-secreting cone cells, which show a more restrictive chromatin profile. This single cell genomics atlas will greatly empower the Drosophila eye as a model system.

genomics↗

bioRxiv2022

Growth Signaling Autonomy in Circulating Tumor Cells Aids Metastatic Seeding

Self-sufficiency (autonomy) in growth signaling, the earliest recognized hallmark of cancer, is fueled by the tumor cells ability to secrete-and-sense growth factors; this translates into cell survival and proliferation that is self-sustained by auto-/paracrine secretion. A Golgi-localized circuitry comprised of two GTPase switches has recently been implicated in the orchestration of growth signaling autonomy. Using breast cancer cells that are either endowed or impaired (by gene editing) in their ability to assemble the circuitry for growth signaling autonomy, here we define the transcriptome, proteome, and phenome of such autonomous state, and unravel its role during cancer progression. We show that autonomy is associated with enhanced molecular programs for stemness, proliferation, and epithelial-mesenchymal plasticity (EMP). Autonomy is both necessary and sufficient for anchorage-independent growth factor-restricted proliferation and resistance to anti-cancer drugs and is required for metastatic progression. Transcriptomic and proteomic studies show that autonomy is associated, with a surprising degree of specificity, to self-sustained EGFR/ErbB signaling. Derivation of a gene expression signature for autonomy revealed that growth signaling autonomy is uniquely induced in circulating tumor cells (CTCs), the harshest phase in the life of tumor cells when it is deprived of biologically available EGF. We also show that autonomy in CTCs tracks therapeutic response and prognosticates outcome. These data support a role for growth signaling autonomy in multiple processes essential for the blood-borne dissemination of human breast cancer. GRAPHIC ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=199 SRC="FIGDIR/small/518910v2_ufig1.gif" ALT="Figure 1"> View larger version (60K): org.highwire.dtl.DTLVardef@167b370org.highwire.dtl.DTLVardef@135b62dorg.highwire.dtl.DTLVardef@14b5e9forg.highwire.dtl.DTLVardef@1311e84_HPS_FORMAT_FIGEXP M_FIG C_FIG Significance StatementA Golgi-localized molecular circuitry has been recently implicated in the orchestration of secrete-and-sense auto-/paracrine loops that impart self-sufficiency in growth signaling, a.k.a., growth signaling autonomy. Using a transdisciplinary approach, this work shows that growth signaling autonomy is uniquely induced in tumor cells that are in circulation. Circulating tumor cells (CTCs) represent a brutish and risky phase in the lifetime of tumor cells when they are exposed to the immune system and hemodynamic sheer forces, all in the setting of growth factor starvation. Cancer cells appear to rely on the autonomy circuit to survive and enhance their fitness to seed metastases. Autonomy generates the kind of eat-what-you-kill entrepreneurial spirit which minimizes the risk of CTCs dying on an otherwise risky journey.

cancer biology↗

bioRxiv2022

Single Cell RNA Sequencing of the Adult Drosophila Eye Reveals Distinct Clusters and Novel Marker Genes for All Major Cell Types

The adult Drosophila eye is a powerful model system for phototransduction and neurodegeneration research. However, single cell resolution transcriptomic data are lacking for this tissue. We present single cell RNA-seq data on 1-day male and female, 3-day and 7-day old male adult eyes, covering early to mature adult eyes. All major cell types, including photoreceptors, cone and pigment cells in the adult eye were captured and identified. Our data sets identified novel cell type specific marker genes, some of which were validated in vivo. R7 and R8 photoreceptors form clusters that reflect their specific Rhodopsin expression and the specific Rhodopsin expression by each R7 and R8 cluster is the major determinant to their clustering. The transcriptomic data presented in this report will facilitate a deeper mechanistic understanding of the adult fly eye as a model system.

genomics↗