Obligate chimerism in male yellow crazy ants

Science (New York, N.Y.)

2023 Apr 07

Darras, H;Berney, C;Hasin, S;Drescher, J;Feldhaar, H;Keller, L;
PMID: 37023182 | DOI: 10.1126/science.adf0419

Multicellular organisms typically develop from a single fertilized egg and therefore consist of clonal cells. We report an extraordinary reproductive system in the yellow crazy ant. Males are chimeras of haploid cells from two divergent lineages: R and W. R cells are overrepresented in the males' somatic tissues, whereas W cells are overrepresented in their sperm. Chimerism occurs when parental nuclei bypass syngamy and divide separately within the same egg. When syngamy takes place, the diploid offspring either develops into a queen when the oocyte is fertilized by an R sperm or into a worker when fertilized by a W sperm. This study reveals a mode of reproduction that may be associated with a conflict between lineages to preferentially enter the germ line.

Single-cell chromatin accessibility identifies enhancer networks driving gene expression during spinal cord development in mouse

Developmental cell

2022 Dec 19

Shu, M;Hong, D;Lin, H;Zhang, J;Luo, Z;Du, Y;Sun, Z;Yin, M;Yin, Y;Liu, L;Bao, S;Liu, Z;Lu, F;Huang, J;Dai, J;
PMID: 36495874 | DOI: 10.1016/j.devcel.2022.11.011

Spinal cord development is precisely orchestrated by spatiotemporal gene regulatory programs. However, the underlying epigenetic mechanisms remain largely elusive. Here, we profiled single-cell chromatin accessibility landscapes in mouse neural tubes spanning embryonic days 9.5-13.5. We identified neuronal-cell-cluster-specific cis-regulatory elements in neural progenitors and neurons. Furthermore, we applied a novel computational method, eNet, to build enhancer networks by integrating single-cell chromatin accessibility and gene expression data and identify the hub enhancers within enhancer networks. It was experimentally validated in vivo for Atoh1 that knockout of the hub enhancers, but not the non-hub enhancers, markedly decreased Atoh1 expression and reduced dp1/dI1 cells. Together, our work provides insights into the epigenetic regulation of spinal cord development and a proof-of-concept demonstration of enhancer networks as a general mechanism in transcriptional regulation.

Clinical Implications and Treatment Strategies for ESR1 Fusions in Hormone Receptor-Positive Metastatic Breast Cancer: A Case Series

The oncologist

2022 Dec 09

Brett, JO;Ritterhouse, LL;Newman, ET;Irwin, KE;Dawson, M;Ryan, LY;Spring, LM;Rivera, MN;Lennerz, JK;Dias-Santagata, D;Ellisen, LW;Bardia, A;Wander, SA;
PMID: 36493359 | DOI: 10.1093/oncolo/oyac248

In hormone receptor-positive metastatic breast cancer (HR+ MBC), endocrine resistance is commonly due to genetic alterations of ESR1, the gene encoding estrogen receptor alpha (ERα). While ESR1 point mutations (ESR1-MUT) cause acquired resistance to aromatase inhibition (AI) through constitutive activation, far less is known about the molecular functions and clinical consequences of ESR1 fusions (ESR1-FUS). This case series discusses 4 patients with HR+ MBC with ESR1-FUS in the context of the existing ESR1-FUS literature. We consider therapeutic strategies and raise the hypothesis that CDK4/6 inhibition (CDK4/6i) may be effective against ESR1-FUS with functional ligand-binding domain swaps. These cases highlight the importance of screening for ESR1-FUS in patients with HR+ MBC while continuing investigation of precision treatments for these genomic rearrangements.

Genes of the coagulation and innate immune system cascade are potentially involved in hepatic graft versus host disease (GvHD) after transcriptomic profiling

Zeitschrift für Gastroenterologie

2022 Jan 01

Qian, Y;Evert, K;Itzel, T;Albin, JE;
| DOI: 10.1055/s-0042-1754738

Background and aims Graft-versus-host-disease (GvHD) is a common complication following allogeneic hematopoietic stem cell transplantation (aHCT) that typically manifests as injury response to the skin, gastrointestinal mucosa and liver. In liver, late onset acute and chronic liver GvHD are more similar to an autoimmune reaction. The identification of valid GvHD biomarker is still an unmet clinical need. In our study, we therefore aimed to identify gene expression patterns, which could be used as potential indicators for the outcome of aHCTs with regard to acute or chronic GvHD. For this purpose, we expect to uncover similar and distinct gene signatures of GvHD in comparison to non-diseased liver tissues and detect potential candidates giving information about the outcome after aHCT. Method Microarray analyses from FFPE samples of patients were performed, and the following criteria were applied: fold change> [1] and a p- value

Identifying Novel Genes and Variants in Immune and Coagulation Pathways Associated with Macular Degeneration

Ophthalmology Science

2022 Aug 01

Huan, T;Cheng, S;Tian, B;Punzo, C;Lin, H;Daly, M;Seddon, J;
| DOI: 10.1016/j.xops.2022.100206

Purpose To select individuals and families with low genetic burden for age-related macular degeneration (AMD), to inform the clinical diagnosis of macular disorders, and to find novel genetic variants associated with macular disease in affected families. Design Genetic association study based on targeted and whole exome sequencing. Participants 758 subjects (481 individuals with maculopathy and 277 controls), including 316 individuals in 72 families. Methods We focused on 150 genes involved in the complement, coagulation, and inflammatory pathways. Single-variant tests were performed on 3062 variants shared among 5 or more subjects using logistic regression. Gene-based tests were used to evaluate aggregate effects from rare and low frequency variants (at minor allele frequency [MAF]

507 CELLULAR PATHWAYS CONTRIBUTING TO FIBROSIS IN THE BLADDER WALL OF CHILDREN WITH EXSTROPHY

Continence

2022 Jun 01

Xie, B;Johal, N;Jabr, R;Kanai, A;Ahmed, A;Fry, C;
| DOI: 10.1016/j.cont.2022.100458

Bladder exstrophy, as part of the exstrophy-epispadias complex, is characterised by a pathologically open and protruding organ. Despite improvements in surgical repair, many patients continue to have poorly contractile, low-capacity bladders. These pathophysiological features are associated with significant fibrosis and greater biomechanical stiffness of the bladder wall (1). The current investigation was designed to yield insight into changes to Wnt-signalling pathways, important in organ and tissue development, but also in the regulation of connective tissue deposition (2). The study used multiplex immunolabelling of target proteins and single mRNA molecules, followed by imaging and unbiased, quantitative image analysis. Data were obtained from children undergoing exstrophy repair and compared to those from children with functionally normal bladders (controls). We hypothesise that exstrophy bladders show excessive connective tissue deposition associated with altered regulation of Wnt-signalling targets.

In Situ Multiplexing to Identify, Quantify, and Phenotype the HIV-1/SIV Reservoir Within Lymphoid Tissue

Methods in molecular biology (Clifton, N.J.)

2022 Jan 05

Busman-Sahay, K;Nekorchuk, MD;Starke, CE;Chan, CN;Estes, JD;
PMID: 34985671 | DOI: 10.1007/978-1-0716-1871-4_19

Modern combination antiretroviral therapy (ART) regimens provide abiding viral suppression for most individuals infected with human immunodeficiency virus (HIV). However, the persistence of viral reservoirs ensures that eradication of HIV-1 (i.e., cure) or sustained ART-free remission (i.e., functional cure) remains elusive, necessitating continual, strict ART adherence and contributing to HIV-1-related comorbidities. Eradication of these viral reservoirs, which persist primarily within lymphoid tissue, will require a deeper understanding of the cellular neighborhoods in which latent and active HIV-1-infected cells reside. By pairing highly sensitive in situ hybridization (ISH) with an exceptionally flexible immunofluorescence (IF) approach, we describe a simple, yet highly adaptable multiplex protocol for investigating the quantity, distribution, and characteristics of HIV-1 viral reservoirs.

Biomarkers in Gynecologic Carcinomas

Biomarkers in Carcinoma of Unknown Primary

2022 Jan 01

Talu, C;Ulukus, E;Zheng, W;
| DOI: 10.1007/978-3-030-84432-5_10

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A novel herpes-like virus inducing branchial lesions in a tiger shark (Galeocerdo cuvier)

Veterinary pathology

2021 Nov 18

Armwood, AR;Stilwell, JM;Ng, TFF;Clauss, TM;Leary, JH;Mader, D;Camus, AC;
PMID: 34794368 | DOI: 10.1177/03009858211052662

A juvenile, male tiger shark (Galeocerdo cuvier) developed illness after capture in Florida waters and was euthanized. Gross lesions included mild skin abrasions, hepatic atrophy, and coelomic fluid. Histologically, gills contained multifocal lamellar epithelial cell necrosis and thromboses. Scattered gill and esophageal epithelial cells had large, basophilic, intracytoplasmic, and intranuclear inclusions. Ultrastructurally, lamellar epithelial cells contained arrays of intracytoplasmic viral particles and scattered intranuclear nucleocapsids. Capsulated virions were 148 ± 11 nm with an 84 ± 8 nm icosahedral nucleocapsid and an electron-dense core. Next-generation sequencing, quantitative polymerase chain reaction, and in situ hybridization performed on formalin-fixed tissue confirmed a herpes-like viral infection. The viral polymerase shared 24% to 31% protein homology with other alloherpesviruses of fish, indicating a divergent virus. This report documents the pathologic findings associated with a molecularly confirmed novel herpes-like virus in an elasmobranch.

Single-cell omics: Overview, analysis, and application in biomedical science

Journal of cellular biochemistry

2021 Aug 30

Stein, CM;Weiskirchen, R;Damm, F;Strzelecka, PM;
PMID: 34459502 | DOI: 10.1002/jcb.30134

Single-cell sequencing methods provide the highest resolution insight into cellular heterogeneity. Owing to their rapid growth and decreasing cost, they are now widely accessible to scientists worldwide. Single-cell technologies enable analysis of a large number of cells, making them powerful tools to characterise rare cell types and refine our understanding of diverse cell states. Moreover, single-cell application in biomedical sciences helps to unravel mechanisms related to disease pathogenesis and outcome. In this Viewpoint, we briefly describe existing single-cell methods (genomics, transcriptomics, epigenomics, proteomics, and mulitomics), comment on available analysis tools, and give examples of method applications in the biomedical field.

Cell-cell contact and signaling in the muscle stem cell niche

Current opinion in cell biology

2021 Aug 02

Kann, AP;Hung, M;Krauss, RS;
PMID: 34352725 | DOI: 10.1016/j.ceb.2021.06.003

Muscle stem cells (also called satellite cells or SCs) rely on their local niche for regulatory signals during homeostasis and regeneration. While a number of cell types communicate indirectly through secreted factors, here we focus on the significance of direct contact between SCs and their neighbors. During quiescence, SCs reside under a basal lamina and receive quiescence-promoting signals from their adjacent skeletal myofibers. Upon injury, the composition of the niche changes substantially, enabling the formation of new contacts that mediate proliferation, self-renewal, and differentiation. In this review, we summarize the latest work in understanding cell-cell contact within the satellite cell niche and highlight areas of open questions for future studies.

Transcriptional and Anatomical Diversity of Medium Spiny Neurons in the Primate Striatum

SSRN Electronic Journal

2021 Apr 02

He, J;Kleyman, M;Chen, J;Alikaya, A;Rothenhoefer, K;Ozturk, B;Wirthlin, M;Fish, K;Byrne, L;Pfenning, A;Stauffer, W;
| DOI: 10.2139/ssrn.3815985

The striatum is the interface between dopamine reward signals and cortico-basal ganglia circuits that mediate diverse behavioral functions. Medium spiny neurons (MSNs) constitute the vast majority of striatal neurons and are traditionally classified as direct- or indirect-pathway neurons. However, that traditional model does not explain the anatomical and functional diversity of MSNs. Here, we defined molecularly distinct MSN types in the primate striatum, including (1) dorsal striatum MSN types associated with striosome and matrix compartments, (2) ventral striatum types associated with the nucleus accumbens shell and olfactory tubercle, and (3) an MSN-like type restricted to μ-opioid receptor rich islands in the ventral striatum. These results lay the foundation for achieving cell type-specific transgenesis in the primate striatum and provide a blueprint for investigating circuit-specific processing.

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	Description
sense Example: Hs-LAG3-sense	Standard probes for RNA detection are in antisense. Sense probe is reverse complent to the corresponding antisense probe.
Intron# Example: Mm-Htt-intron2	Probe targets the indicated intron in the target gene, commonly used for pre-mRNA detection
Pool/Pan Example: Hs-CD3-pool (Hs-CD3D, Hs-CD3E, Hs-CD3G)	A mixture of multiple probe sets targeting multiple genes or transcripts
No-XSp Example: Hs-PDGFB-No-XMm	Does not cross detect with the species (Sp)
XSp Example: Rn-Pde9a-XMm	designed to cross detect with the species (Sp)
O# Example: Mm-Islr-O1	Alternative design targeting different regions of the same transcript or isoforms
CDS Example: Hs-SLC31A-CDS	Probe targets the protein-coding sequence only
EnEm	Probe targets exons n and m
En-Em	Probe targets region from exon n to exon m
Retired Nomenclature
tvn Example: Hs-LEPR-tv1	Designed to target transcript variant n
ORF Example: Hs-ACVRL1-ORF	Probe targets open reading frame
UTR Example: Hs-HTT-UTR-C3	Probe targets the untranslated region (non-protein-coding region) only
5UTR Example: Hs-GNRHR-5UTR	Probe targets the 5' untranslated region only
3UTR Example: Rn-Npy1r-3UTR	Probe targets the 3' untranslated region only
Pan Example: Pool	A mixture of multiple probe sets targeting multiple genes or transcripts

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