Biology subjects

Babaei, S.

Publications and source records attributed to Babaei, S..

7 recordsLinked to original sources

bioRxiv2026

Transcriptomic analysis of organotypic porcine retina cultures

Porcine organotypic retinal explant cultures are widely used to study retinal neurodegeneration under controlled conditions, but the biological process that occurs in the retinal explant over time due to preparation-induced injury and culture are not well understood. Here, we generated a time-resolved transcriptomic reference for porcine neural retinal explants-maintained ex vivo for 10 days. Global expression profiles are strongly separated by culture time, with Day 0 clearly distinct from cultured samples and at Day 7 and Day 10 showing the highest similarity, indicating a transition toward a later stabilized state. Across the time course, 3,187 genes were differentially expressed relative to Day 0, with the largest shifts occurring at an early stage of culture (Day 1-Day 3). Pathway-level analyses revealed coordinated remodeling involving inflammatory signaling, and metabolic/bioenergetic changes, including reduced mitochondrial and oxidative phosphorylation-related programs at later time points. Here, we provide a time-resolved transcriptomics reference dataset for cultured porcine retinal explants. These data can build a foundation to interpret data generated in this model, differentiate changes inherent to the explant culture from treatment-specific effects and to select appropriate experimental windows for mechanistic studies of retinal degeneration.

molecular biology↗

bioRxiv2024

Multiplex PCR reveals population structure in an inbred communal bird.

We sampled communally breeding p[u]keko (Porphyrio melanotus melanotus, family Rallidae) populations on the North (T[a]wharanui Park) and South (Otokia Reserve) Islands of New Zealand that differ in climate and ecology. North Island populations have year-round territories, philopatry, and form kin groups, resulting in inbreeding. South Island populations have seasonal territories, high dispersal rates, and form non-kin groups, leading to outbreeding. Given behavioural evidence of inbreeding we predicted that the North Island population would exhibit lower heterozygosity and higher inbreeding coefficients than the South Island population. We hypothesized that the South Island population originated via a range expansion from the north and predicted that South Island birds would have lower allelic diversity due to founder effects. To test these predictions, we developed microsatellite primers, optimized multiplex PCRs, and genotyped breeding groups from the North and South Island. Breeding groups from North Island were genetically differentiated, whereas population structure was not detected in the South Island birds. North Island birds had higher inbreeding coefficients and levels of within group kinship, but not allelic diversity, compared to South Island birds. Our results are thus inconclusive about whether the South Island population originated via a range expansion from the north. This pilot study validated microsatellite markers and PCR methods and is the first genetic analysis of population structure and relatedness within communal breeding p[u]keko groups. These genetic tools will be used for larger-scale studies to help resolve the origins of the South Island population and provide further insights into the effects of ecology and behaviour on inbreeding, reproductive success, and population demographics in this species. P[u]keko may provide an excellent model for experimental analyses of inbreeding effects on wild avian populations without the attendant concerns that come with small, endangered populations. This work may thus inform conservation efforts, including translocations of endangered species.

genetics↗

bioRxiv2023

S3-CIMA: Supervised spatial single-cell image analysis for the identification of disease-associated cell type compositions in tissue

The spatial organization of various cell types within the tissue microenvironment is a key element for the formation of physiological and pathological processes, including cancer and autoimmune diseases. Here, we present S3-CIMA, a weakly supervised convolutional neural network model that enables the detection of disease-specific microenvironment compositions from high-dimensional proteomic imaging data. We demonstrate the utility of this approach by determining cancer outcome- and cellular signaling-specific spatial cell state compositions in highly multiplexed fluorescence microscopy data of the tumor microenvironment in colorectal cancer. Moreover, we use S3-CIMA to identify disease onset-specific changes of the pancreatic tissue microenvironment in type 1 diabetes using imaging mass cytometry data. We evaluated S3-CIMA as a powerful tool to discover novel disease-associated spatial cellular interactions from currently available and future spatial biology datasets.

bioinformatics↗

bioRxiv2022

Circular RNAs are Associated with Floral Fate Acquisition in soybean shoot apical meristem

Soybean (Glycine max), a major oilseed and protein source, requires a short-day photoperiod for floral induction. Though key transcription factors controlling flowering have been identified, the role of the non-coding (dark) genome is limited. circular RNAs (circRNAs) recently emerged as a novel class of RNAs with critical regulatory functions. However, a study on circRNAs during the floral transition of a crop plant is lacking. We investigated the expression and potential function of circRNAs in floral fate acquisition by soybean shoot apical meristem in response to short-day treatment. Using deep sequencing and in-silico analysis, we denoted 384 circRNAs, with 129 exhibiting short-day treatment-specific expression patterns. We also identified 38 circRNAs with predicted binding sites for miRNAs that could affect the expression of diverse downstream genes through the circRNA-miRNA-mRNA network. Notably, four different circRNAs with potential binding sites for an important microRNA module regulating developmental phase transition in plants, miR156 and miR172, were identified. We also identified circRNAs arising from hormonal signaling pathway genes, especially abscisic acid, and auxin, suggesting an intricate network leading to floral transition. This study highlights the gene regulatory complexity during the vegetative to reproductive transition and paves the way to unlock floral transition in a crop plant. HighlightA new class of regulatory RNAs, circular RNAs, modulate floral transition in a crop plant, soybean, by regulating hormonal pathways and post-transcriptional processes.

plant biology↗

bioRxiv2021

Non-coding circular RNAs repertoire and expression profile during Brassica rapa pollen development

Circular RNAs (circRNAs) are covalently closed long non-coding RNA (lncRNA) molecules generated by the back-splicing of exons from linear precursor mRNAs. Though linear lncRNAs have been shown to play important regulatory roles in diverse biological and developmental processes, little is known about the role of their circular counterparts. In this study, we have performed high-throughput RNA sequencing to delineate the expression profile and potential function of circRNAs during the five stages of pollen development in Brassica rapa. A total of 1180 circRNAs were detected in pollen development, of which 367 showed stage-specific expression patterns. Functional enrichment and metabolic pathway analysis showed that the parent genes of circRNAs were mainly involved in pollen-related molecular and biological processes such as mitotic and meiosis cell division, DNA processes, protein synthesis, protein modification, and polysaccharide biosynthesis. Moreover, by predicting the circRNA-miRNA network from our differentially expressed circRNAs, we found 88 circRNAs with potential miRNA binding sites suggesting their role in post-transcriptional regulation of the genes. Finally, we confirmed the back-splicing sites of 9 randomly selected circRNAS using divergent primers and Sanger sequencing. Our study presents the first systematic analysis of circular RNAs during pollen development and forms the basis of future studies for unlocking complex gene regulatory networks underpinning reproduction in flowering plants.

molecular biology↗

bioRxiv2020

Genome-wide identification and comparative analysis of Dof gene family in Brassica napus

DOF, DNA binding with one finger proteins are plant-specific transcription factors shown to play roles in diverse plant functions. However, a--little is known about DOF protein repertoire of the allopolyploid crop, Brassica napus. Here, we report genome-wide identification and systematic analysis of the Dof transcription factor family in this important oilseed crop. We identified 117 Brassica napus Dof genes (BnaDofs). So far, this is the largest number of Dof genes reported in a single eudicot species. Based on phylogenetic analysis, BnaDofs were classified into nine groups (A, B1, B2. C1, C2.1, C2.2, C3, D1, D2). Most members belonging to a particular group displayed conserved gene structural organisation and similar protein motifs distribution. Chromosomal localisation analysis highlighted the uneven distribution of BnaDofs across all chromosomes. Evolutionary analysis exemplified that the divergence of Brassica genus from Arabidopsis, the whole genome triplication event, and the hybridisation of B. oleracea and B. rapa to form B. napus, followed by gene loss and rearrangements, led to the expansion and divergence of Dof TF gene family in B. napus. Functional annotation of BnaDof proteins, cis-element analysis of their promoters suggested potential roles in organ development, the transition from vegetative to the reproductive stage, light responsiveness, phytohormone responsiveness as well as abiotic stress responses. Furthermore, the transcriptomic analysis highlighted the preferential tissue-specific expression patters of BnaDofs and their role in response to various abiotic stress. Overall, this study provides a comprehensive understanding of the molecular structure, evolution, and potential functional roles of Dof genes in plant development and abiotic stress response.

plant biology↗

bioRxiv2020

Genome-wide CRISPR and small-molecule screens uncover targetable dependencies in ATRT

Atypical teratoid rhabdoid tumors (ATRT) are incurable high-grade pediatric brain tumors. Concepts for molecular-driven therapies in ATRTs lag behind, mainly due to the absence of actionable genetic alterations. We performed genome-wide CRISPR/Cas9 knockout screens in six human ATRT cell lines and identified a total of 671 context-specific essential genes. Based on these genetic dependencies, we constructed a library of small-molecule inhibitors that we found to preferentially inhibit growth of ATRT cells. CDK4/6 inhibitors, among the most potent drugs in our library, are capable of inhibiting tumor growth due to mutual exclusive dependency of ATRTs on CDK4 or CDK6. These distinct dependencies drive heterogeneity in response to CDK4/6 inhibitors in ATRTs. Our approach might serve as a blueprint for fostering the identification of functionally-instructed therapeutic strategies in other incurable diseases beyond ATRT, whose genomic profiles also lack actionable alterations so far.

cancer biology↗