In developmental toxicity testing, in vitro screening assays are highly needed to increase efficiency and to reduce animal use. A promising in vitro assay is the cardiac embryonic stem cell test (ESTc), in which the effect of developmental toxicants on cardiomyocyte differentiation is assessed. Recently, we developed a neural differentiation variant of the stem cell test (neural embryonic stem cell test [ESTn]). In both of these models, we have previously performed a series of transcriptomic studies to characterize gene expression changes (1) across time during normal differentiation and (2) in response to a series of developmental toxicants in the ESTn and ESTc. Here, using the cumulative of these studies, we compared gene expression profiles of ESTn and ESTc over time as well as model-specific changes induced by seven compounds, comprising six known in vivo developmental toxicants and one negative control. Time-related gene expression profiles showed similarities between the two EST systems. However, specific genes could be identified changing over time differently in each model related to the two different lineages of differentiation. Interestingly, compound-induced gene expression changes were generally model specific, especially for methylmercury and flusilazole, which were predicted better in ESTn and ESTc, respectively. Valproic acid-induced gene expression changes were most comparable out of the six developmental toxicants between the ESTn and ESTc. Direct transcriptomic comparisons between the ESTn and ESTc indicate that combined transcriptomic analyses support and complement each other. Therefore, a combined approach incorporating ESTc and ESTn may improve developmental toxicant detection over individual assays.

Developmental toxicity

Toxicant

10.1093/toxsci/kfs333

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Citations (42)

Screening of Oryza species for rice water weevil resistance

Elaine Maytag Nowick Joshua F. Robinson

Oryza

Rice water

Source

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Global proteomic analyses of human cytotrophoblast differentiation/invasion

Development (2021)

Hao Chen Katherine E. Williams Elaine Kwan Mirhan Kapidzic Kenisha A. Puckett

During human pregnancy, cytotrophoblasts (CTBs) from the placenta differentiate into specialized subpopulations that play crucial roles in proper fetal growth and development. A subset of these CTBs differentiate along an invasive pathway, penetrating the decidua and anchoring the placenta to the uterus. A crucial hurdle in pregnancy is the ability of these cells to migrate, invade and remodel spiral arteries, ensuring adequate blood flow to nourish the developing fetus. Although advances continue in describing the molecular features regulating the differentiation of these cells, assessment of their global proteomic changes at mid-gestation remain undefined. Here, using sequential window acquisition of all theoretical fragment-ion spectra (SWATH), which is a data-independent acquisition strategy, we characterized the protein repertoire of second trimester human CTBs during their differentiation towards an invasive phenotype. This mass spectrometry-based approach allowed identification of 3026 proteins across four culture time points corresponding to sequential stages of differentiation, confirming the expression dynamics of established molecules and offering new information into other pathways involved. The availability of a SWATH CTB global spectral library serves as a beneficial resource for hypothesis generation and as a foundation for further understanding CTB differentiation dynamics.

Cytotrophoblast

CTBS

Decidua

10.1242/dev.199561

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Citations (7)

Euphytica (1997)

Joshua F. Robinson Marja Jalli

10.1023/a:1002996722383

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Placental Malaria Induces a Unique Placental Methylation Profile Associated With Fetal Growth Restriction

American Journal of Obstetrics and Gynecology (2024)

Nida Özarslan Corina Mong John Ategeka Xiaogang Li Sirirak Buarpung

Fetal growth

Intrauterine growth restriction

10.1016/j.ajog.2024.09.032

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Euphytica (1999)

Joshua F. Robinson

Epistasis

Doubled haploidy

10.1023/a:1003749412317

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Field Resistance to Russian Wheat Aphid in Barley: II. Yield Assessment

Crop Science (1991)

D. S. Calhoun P. A. Burnett Joshua F. Robinson H. Vivar L. Gilchrist

Host‐plant resistance could reduce yield losses due to feeding of Russian wheat aphid (RWA), Diuraphis noxia (Mordvilko), on barley ( Hordeum vulgare L.). Most RWA screening procedures rely on differential expression of foliar RWA feeding symptoms identify resistant genotypes. This study was conducted to determine if field expression of foliar symptoms in barley is a good indicator of yield reduction due to RWA feeding damage. Spring barley genotypes representing a range in foliar symptom expression were evaluated in the field in infested and uninfested hill‐plots in summer 1989( 14 genotypes) and winter 1990 (19 genotypes). Plants were scored for foliar symptoms on a 1 to 6 scale (1 = no symptoms). Grain yield (GY), spike number (SN), 100‐kernel weight (KW), and yield (SY, 1990 only) were measured. Reduction in GY among genotypes due to RWA feeding ranged from −10 to 48%i n 1989 and from −17 to 59% in 1990, and was highly correlated ( r = 0.71, df = 31, P < 0.01) with foliar symptom scores. Reduction in SN ranged from −3 to 42% in 1989 and from −14 to 39% in 1990, and was also highly correlated ( r = 0.77, df = 31, P < 0.01)) with foliar symptom scores. Kernel weight was unaffected by RWiAn festation. Reduction in SY ranged from −16 to 43% and was correlated ( r = 0.65, df 17, P < 0.01) with foliar symptom scores. Visual rating based on foliar RWA feeding symptoms in artificially infested hill‐plots in the field was an effective method to identify genotypes that show minimal yield reduction under RWA infestation.

Russian wheat aphid

10.2135/cropsci1991.0011183x003100060015x

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RosetteArray Platform for Quantitative High-Throughput Screening of Human Neurodevelopmental Risk

bioRxiv (Cold Spring Harbor Laboratory) (2024)

Brady F. Lundin Gavin Knight Nikolai J. Fedorchak Kevin Krucki Nisha Iyer

SUMMARY Neural organoids have revolutionized how human neurodevelopmental disorders (NDDs) are studied. Yet, their utility for screening complex NDD etiologies and in drug discovery is limited by a lack of scalable and quantifiable derivation formats. Here, we describe the RosetteArray ® platform’s ability to be used as an off-the-shelf, 96-well plate assay that standardizes incipient forebrain and spinal cord organoid morphogenesis as micropatterned, 3-D, singularly polarized neural rosette tissues (>9000 per plate). RosetteArrays are seeded from cryopreserved human pluripotent stem cells, cultured over 6-8 days, and immunostained images can be quantified using artificial intelligence-based software. We demonstrate the platform’s suitability for screening developmental neurotoxicity and genetic and environmental factors known to cause neural tube defect risk. Given the presence of rosette morphogenesis perturbation in neural organoid models of NDDs and neurodegenerative disorders, the RosetteArray platform could enable quantitative high-throughput screening (qHTS) of human neurodevelopmental risk across regulatory and precision medicine applications.

Organoid

Forebrain

10.1101/2024.04.01.587605

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Citations (2)