Biology subjects

Ilnytskyy, Y.

Publications and source records attributed to Ilnytskyy, Y..

3 recordsLinked to original sources

bioRxiv2021

Plagl1 is part of the mammalian retinal injury response and a critical regulator of Muller glial cell quiescence

Retinal damage triggers reactive gliosis in Muller glia across vertebrate species, but only in regenerative animals, such as teleost fish, do Muller glia initiate repair; proliferating and undergoing neurogenesis to replace lost cells. By mining scRNA-seq and bulk RNA-seq datasets, we found that Plagl1, a maternally imprinted gene, is dynamically regulated in reactive Muller glia post-insult, with transcript levels transiently increasing before stably declining. To study Plagl1 retinal function, we examined Plagl1+/-pat null mutants postnatally, revealing defects in retinal architecture, visual signal processing and a reactive gliotic phenotype. Plagl1+/-pat Muller glia proliferate ectopically and give rise to inner retinal neurons and photoreceptors. Transcriptomic and ATAC-seq profiles revealed similarities between Plagl1+/-pat retinas and neurodegenerative and injury models, including an upregulation of pro-gliogenic and pro-proliferative pathways, such as Notch, not observed in wild-type retinas Plagl1 is thus an essential component of the transcriptional regulatory networks that retain mammalian Muller glia in quiescence.

neuroscience↗

bioRxiv2020

Multigenerational exposure to heat stress induces phenotypic resilience, and genetic and epigenetic variations in Arabidopsis thaliana offspring

Plants are sedentary organisms that constantly sense changes in their environment and react to various environmental cues. On a short-time scale, plants respond through alterations in their physiology, and on a long-time scale, plants alter their development and pass on the memory of stress to the progeny. The latter is controlled genetically and epigenetically and allows the progeny to be primed for future stress encounters, thus increasing the likelihood of survival. The current study intended to explore the effects of multigenerational heat stress in Arabidopsis thaliana. 25 generations of Arabidopsis thaliana were propagated in the presence of heat stress. The multigenerational stressed lineage F25H exhibited a higher tolerance to heat stress and elevated frequency of homologous recombination, as compared to the parallel control progeny F25C. A comparison of genomic sequences revealed that the F25H lineage had a three-fold higher number of mutations (SNPs and INDELs) as compared control lineages, suggesting that heat stress induced genetic variations in the heat-stressed progeny. The F25H stressed progeny showed a 7-fold higher number of non-synonymous mutations than the F25C line. Methylome analysis revealed that the F25H stressed progeny showed a lower global methylation level in the CHH context than the control progeny. The F25H and F25C lineages were different from the parental control lineage F2C by 66,491 and 80,464 differentially methylated positions (DMPs), respectively. F25H stressed progeny displayed higher frequency of methylation changes in the gene body and lower in the body of transposable elements (TEs). Gene Ontology analysis revealed that CG-DMRs were enriched in processes such as response to abiotic and biotic stimulus, cell organizations and biogenesis, and DNA or RNA metabolism. Hierarchical clustering of these epimutations separated the heat stressed and control parental progenies into distinct groups which revealed the non-random nature of epimutations. We observed an overall higher number of epigenetic variations than genetic variations in all comparison groups, indicating that epigenetic variations are more prevalent than genetic variations. The largest difference in epigenetic and genetic variations was observed between control plants comparison (F25C vs F2C), which clearly indicated that the spontaneous nature of epigenetic variations and heat-inducible nature of genetic variations. Overall, our study showed that progenies derived from multigenerational heat stress displayed a notable adaption in context of phenotypic, genotypic and epigenotypic resilience.

plant biology↗

bioRxiv2020

Proneural genes define ground state rules to regulate neurogenic patterning and cortical folding

Transition from smooth, lissencephalic brains to highly-folded, gyrencephalic structures is associated with neuronal expansion and breaks in neurogenic symmetry. Here we show that Neurog2 and Ascl1 proneural genes regulate cortical progenitor cell differentiation through cross-repressive interactions to sustain neurogenic continuity in a lissencephalic rodent brain. Using in vivo lineage tracing, we found that Neurog2 and Ascl1 expression defines a lineage continuum of four progenitor pools, with double+ progenitors displaying several unique features (least lineage-restricted, complex gene regulatory network, G2 pausing). Strikingly, selective killing of double+ progenitors using split-Cre;Rosa-DTA transgenics breaks neurogenic symmetry by locally disrupting Notch signaling, leading to cortical folding. Finally, consistent with NEUROG2 and ASCL1 driving discontinuous neurogenesis and folding in gyrencephalic species, their transcripts are modular in folded macaque cortices and pseudo-folded human cerebral organoids. Neurog2/Ascl1 double+ progenitors are thus Notch-ligand expressing niche cells that control neurogenic periodicity to determine cortical gyrification. HIGHLIGHTSO_LINeurog2 and Ascl1 expression defines four distinct transitional progenitor states C_LIO_LIDouble+ NPCs are transcriptionally complex and mark a lineage branch point C_LIO_LIDouble+ NPCs control neurogenic patterning and cortical folding via Notch signaling C_LIO_LINeurog2 and Ascl1 expression is modular in folded and not lissencephalic cortices C_LI eTOC BLURBEmergence of a gyrencephalic cortex is associated with a break in neurogenic continuity across the cortical germinal zone. Han et al. identify a pool of unbiased neural progenitors at a lineage bifurcation point that co-express Neurog2 and Ascl1 and produce Notch ligands to control neurogenic periodicity and cortical folding.

developmental biology↗