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Search indexed bioRxiv preprints in genomics, neuroscience, cell biology and bioinformatics. Read source abstracts and check manuscript versions; preprints are not peer reviewed.

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bioRxiv2018

Are populations like a circuit? The relationship between isolation by distance and isolation by resistance

A number of methods commonly used in landscape genetics use an analogy to electrical resistance on a network to describe and fit barriers to movement across the landscape using genetic distance data. These are motivated by a mathematical equivalence between electrical resistance between two nodes of a network and the \"commute time\", which is the mean time for a random walk on that network to leave one node, visit the other, and return. However, genetic data are more accurately modeled by a different quantity, the coalescence time. Here, we describe the differences between resistance distance and coalescence time, and explore the consequences for inference. We implement a Bayesian method to infer effective movement rates and population sizes under both these models, and find that inference using commute times can produce misleading results in the presence of biased gene flow. We then use forwards-time simulation with continuous geography to demonstrate that coalescence-based inference remains more accurate than resistance-based methods on realistic data, but difficulties highlight the need for methods that explicitly model continuous, heterogeneous geography.

evolutionary biology↗

bioRxiv2018

INPP5E controls ciliary localization of phospholipids and odor response kinetics in a mouse model of Joubert syndrome

Ciliopathies manifested in part by a dysfunction of several phosphoinositide 5phosphatases constitute Lowes, Dent disease 2 and Joubert syndromes through critical involvement of properly functioning primary cilia (PC). We showed that deletion of INPP5E under the control of OMP-Cre in mature mouse olfactory sensory neurons (OSNs) led to a dramatic redistribution of PI(4,5)P2 (PIP2) in cilia, significant reduction of PI(3,4)P2 and enrichment of PI(3,4,5)P3 in knobs. Redistribution of the phospholipids accompanied marked elongation of cilia in INPP5E-OMP knockout (KO) OSNs. Such a dramatic remodeling of phospholipid composition however did not affect other integral membrane lipids (cholesterol, sphingomyelin, glycosylated phosphaditylinositol, phosphatidylserine). Proteins known to bind with high affinity PIP2 entered the cilia of the KO OSNs. Loss of INPP5E did not affect ciliary localization of endogenous olfactory receptor M71/M72 or distribution and movement of IFT122 particles implicating independent of phospholipids mechanism of retrograde protein transport in cilia of mature OSNs. Net odor sensitivity and response magnitude as measured by EOG was not affected by the mutation. However, odor adaptation in the KO mouse was significantly impaired resulting in less efficient recovery and altered inactivation kinetics of the odor response at the EOG and single-cell level. These findings implicate phosphoinositide-dependent regulation of active Ca2+ extrusion in OSNs whereby controlling the rate of sensory adaptation.\n\nSignificance statementCurrently there are little if any available treatment to cure congenital ciliopathies. This is in part due to lack of basic knowledge of cilia biology. Olfactory cilia as well as primary cilia appear to be a phospholipid privileged organelle distinct from the rest of plasma membrane albeit sharing its continuity. We characterized distribution of several critically important for cell biology phospholipids and showed that their balance, especially of PIP2, is disrupted in Joubert syndrome animal model and has functional implications. Virally assisted delivery of wild type INPP5E to the mutant OSNs was able to restore localization of PIP2 and rescued impaired response to odor.

neuroscience↗

bioRxiv2018

Loss of ZnT8 function protects against diabetes by enhanced insulin secretion

A rare loss-of-function variant p.Arg138* in SLC30A8 encoding the zinc transporter 8 (ZnT8) enriched in Western Finland protects against type 2 diabetes (T2D). We recruited relatives of the identified carriers and showed that protection was associated with better insulin secretion due to enhanced glucose responsiveness and proinsulin conversion, especially compared with individuals matched for the genotype of a common T2D risk variant in SLC30A8, p.Arg325. In genome-edited human IPS-derived {beta}-like cells, we establish that the p.Arg138* variant results in reduced SLC30A8 expression due to haploinsufficiency. In human {beta}-cells loss of SLC30A8 leads to increased glucose responsiveness and reduced KATP channel function, which was also seen in isolated islets from carriers of the T2D-protective allele p.Trp325. These data position ZnT8 as an appealing target for treatment aiming at maintaining insulin secretion capacity in T2D.

genetics↗

bioRxiv2018

Genome sequence of the corn leaf aphid (Rhopalosiphum maidis Fitch)

BackgroundThe corn leaf aphid (Rhopalosiphum maidis Fitch) is the most economically damaging aphid pest on maize (Zea mays), one of the worlds most important grain crops. In addition to causing direct damage due to the removal of photoassimilates, R. maidis transmits several destructive maize viruses, including Maize yellow dwarf virus, Barley yellow dwarf virus, Sugarcane mosaic virus, and Cucumber mosaic virus.\n\nFindingsA 326-Mb genome assembly of BTI-1, a parthenogenetically reproducing R. maidis clone, was generated with a combination of PacBio (208-fold coverage) and Illumina sequencing (80-fold coverage), which contains a total of 689 contigs with an N50 size of 9.0 Mb. The contigs were further clustered into four scaffolds using the Phase Genomics Hi-C interaction maps, consistent with the commonly observed 2n = 8 karyotype of R. maidis. Most of the assembled contigs (473 spanning 321 Mb) were successfully orientated in the four scaffolds. The R. maidis genome assembly captured the full length of 95.8% of the core eukaryotic genes, suggesting that it is highly complete. Repetitive sequences accounted for 21.2% of the assembly, and a total of 17,647 protein-coding genes were predicted in the R. maidis genome with integrated evidence from ab initio and homology-based gene predictions and transcriptome sequences generated with both PacBio and Illumina. An analysis of likely horizontally transferred genes identified two from bacteria, seven from fungi, two from protozoa, and nine from algae.\n\nConclusionsA high-quality R. maidis genome was assembled at the chromosome level. This genome sequence will enable further research related to ecological interactions, virus transmission, pesticide resistance, and other aspects of R. maidis biology. It also serves as a valuable resource for comparative investigation of other aphid species.

genomics↗

bioRxiv2018

Climate explains recent population divergence, introgression and persistence in tropical mountains: phylogenomic evidence from Atlantic Forest warbling finches

Taxa with disjunct distributions are common in montane biotas and offer excellent opportunities to investigate historical processes underlying genetic and phenotypic divergence. In this context, subgenomic datasets offer novel opportunities to explore historical demography in detail, which is key to better understand the origins and maintenance of diversity in montane regions. Here we used a large ultraconserved elements dataset to get insights into the main biogeographic processes driving the evolution of the Montane Atlantic Forest biota. Specifically, we studied two species of warbling finches disjunctly distributed across a region of complex geological and environmental history. We found that a scenario of three genetically differentiated populations is best supported by genomic clustering methods. Also, demographic simulations support simultaneous isolation of these populations at ~10 kya, relatively stable population sizes over recent time, and recent gene flow. Our results suggest a dual role of climate: population divergence, mediated by isolation in mountain tops during warm periods, as well as population maintenance - allowing persistence mediated by shifts in elevation distribution during periods of climate change, with episodic bouts contact and gene flow. Additional support for the role of climate comes from evidence of their contact in a recent past. We propose that two major gaps, which we call Sao Paulo and Caparao subtropical gaps, have been historically important in the divergence of cold adapted organisms in the Atlantic Forest, and could be associated to cryptic diversity. Finally, our results suggest that shallow divergence and past gene flow may be common in montane organisms, but complex demographic histories may be detectable only when using subgenomic or genomic datasets.

evolutionary biology↗

bioRxiv2018

Evolution of hominin detoxification: Neanderthal and modern human AHR respond similarly to TCDD

In studies of hominin adaptations to fire use, the role of the aromatic hydrocarbon receptor (AHR) in the evolution of hominin detoxification, especially regarding toxic smoke components, has been highlighted, including statements that the modern human AHR is significantly better at dealing with smoke toxins. We compared the AHR-controlled induction of cytochrome P450 1A1 (CYP1A1) in cultured cells transfected with an Altai-Neanderthal respectively a modern human reference AHR expression construct, and exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). We compared the complete AHR mRNA sequences including the untranslated regions (UTRs), maintaining the original codon usage, in HeLa human cervix epithelial adenocarcinoma cells. Our experiments complement a previous study of the AHR coding region optimized for mammalian codon usage and expressed in rat cells. Our results show no significant difference in CYP1A1 induction by TCDD between Neanderthal and modern human AHR (instead of a previously reported 150-1000 times difference range before), demonstrating that expression in a homologous cellular background is of major importance. The two dose-response curves almost coincide, except for a higher extrapolated maximum induction level for the Neanderthal AHR, possibly caused by a 5-UTR G-variant known from modern humans (rs7796976). Our results are strongly at odds with a major role of the modern human AHR in the evolution of hominin detoxification of smoke components and consistent with our previous study which concluded that efficient detoxification alleles are more dominant in ancient hominins than in modern humans based on 18 relevant genes in addition to AHR.

evolutionary biology↗

bioRxiv2018

The TMCrys server for supporting crystallization of transmembrane proteins

MotivationDue to their special properties, the structures of transmembrane proteins are extremely hard to determine. Several methods exist to predict the propensity of successful completion of the structure determination process. However, available predictors incorporate data of any kind of proteins, hence they can hardly differentiate between crystallizable and non-crystallizable membrane proteins.\n\nResultsWe implemented a web server to simplify running TMCrys prediction method that was developed specifically to separate crystallizable and non-crystallizable proteins.\n\nAvailabilityhttp://tmcrys.enzim.ttk.mta.hu\n\nContacttusnady.gabor@ttk.mta.hu\n\nvarga.julia@ttk.mta.hu

bioinformatics↗

bioRxiv2018

MicroED data collection with SerialEM

We developed a procedure for the cryoEM method MicroED using SerialEM. With this approach, SerialEM coordinates stage rotation, microscope operation, and camera functions for automated continuous-rotation MicroED data collection. More than 300 datasets can be collected overnight in this way, facilitating high-throughput MicroED data collection for large-scale data analyses.

biophysics↗

bioRxiv2018

IgA-deficient humans exhibit gut microbiota dysbiosis despite production of compensatory IgM

Immunoglobulin A is the dominant antibody isotype found in mucosal secretions and enforces host-microbiota symbiosis in mice, yet selective IgA-deficiency (sIgAd) is the most common primary immunodeficiency in humans and is often described as asymptomatic. Here, we determined the effects of IgA deficiency on human gut microbiota composition and evaluated the possibility that secretion of IgM can compensate for a lack of secretory IgA. We used 16S rRNA gene sequencing and bacterial cell sorting to evaluate gut microbiota composition and IgA or IgM coating of the gut microbiota in 15 sIgAd subjects and 15 matched controls. Although sIgAd subjects secreted a significant amount of IgM into the intestinal lumen, this was insufficient to fully compensate for the lack of secretory IgA. Indeed, sIgAd subjects displayed an altered gut microbiota composition as compared to healthy controls, which was characterized by a trend towards decreased overall microbial diversity and significant shifts in the relative abundances of specific microbial taxa. While IgA targets a defined subset of the microbiota via high-level coating, compensatory IgM binds a broader subset of the microbiota in a less targeted manner. We conclude that IgA plays a critical and non-redundant role in controlling gut microbiota composition in humans and that secretory IgA has evolved to maintain a diverse and stable gut microbial community that promotes human health, enhances resistance to infection, and is resilient to perturbation.

immunology↗

bioRxiv2018

mTORC1 Restricts Hepatitis C Virus Replication Through ULK1-mediated Suppression of miR-122 and Facilitates Post-replication Events

Mechanistic target of rapamycin (mTOR) is an important kinase that assimilates several upstream signals including viral infection and facilitates appropriate response by the cell through two unique complexes mTORC1 and mTORC2. Here, we demonstrate that mTORC1 is activated early during HCV infection as antiviral response. Pharmacological inhibition of mTORC1 promoted HCV replication as suggested by elevated levels of HCV (+) and (-) RNA strands. This was accompanied by significant drop in extracellular HCV RNA levels indicating defective post-replication stages. The increase in viral RNA levels failed to augment intracellular infectious virion levels, suggesting that mTORC1 inhibition is detrimental to post-replication steps. Lower infectivity of the supernatant confirmed this observation. Depletion of Raptor and ULK1 accurately reproduced these results suggesting that mTORC1 imparted these effects on HCV through mTORC1-ULK1 arm. Interestingly, ULK1 depletion resulted in increased levels of miR-122, a critical host factor for HCV replication, thus revealing a new mechanism of regulation by ULK1. The binary effect of mTORC1 on HCV replication and egress suggests that mTORC1-ULK1 could be critical in replication: egress balance. Interestingly we discover that ULK1 depletion did not interfere with autophagy in Huh7.5 cells and hence the effects on HCV replication and post-replication events are not resultant of involvement of autophagy. Our studies demonstrate an overall ULK1 mediated anti-HCV function of mTORC1 and identifies an ULK1-independent autophagy that allows HCV replication in spite of mTORC1 activation.

microbiology↗

bioRxiv2018

Reconstructing the origins of the space-number association: spatial and number-magnitude codes must be used jointly to elicit spatially organised mental number lines.

In a series of recent studies we have pointed out that the use of contrasting left/right spatial codes, whether indirectly related to number magnitudes through response selection or directly associated to the same magnitudes to guide their spatial positioning on a mental number line, is crucial in eliciting space-number associations (Aiello, 2012; Fattorini et al., 2015; 2016; Pinto et al., 2018). Nonetheless, this conclusion is based on experiments in which spatial and number-magnitudes codes are used jointly during task performance. Here, in a series of unimanual Go/No-Go tasks with intermixed central numerical and pictorial targets, i.e. arrows pointing to the left or to the right, we explore whether spatial codes used in isolation inherently evoke the left-to-right representation of number magnitudes and, vice-versa, whether number-magnitude codes used in isolation inherently evoke the conceptual activation of left/right spatial codes. In a first series of experiments participants were asked to provide unimanual Go/N-Go responses based on instructions that activated only magnitude codes, e.g. \"push only if the number is lower than 5 and whenever an arrow appears\", or only spatial codes, e.g. \"push only when an arrow points to the left and whenever a number appears\". In a second series of experiments, the same numerical instructions were combined with the request of responding only to arrows in a specific colour, e.g. \"push when the number is lower than 5 and whenever a blue arrow appears\". At variance with a recent experiment by Shaki and Fischer (2018), in our experiments no constant association was present between a specific arrow colour and a specific arrow direction. The results of these experiments highlight no space-number congruency effects: e.g. no faster RTs to arrows pointing to the left rather than to the right when participants attend to numbers lower than 5 and, vice-versa, no faster RTs to numbers lower than 5 rather than higher, when participants attend to arrows pointing to the left. Based on these findings it must be concluded that neither space codes used in isolation can elicit a spatial representation of number magnitudes nor number-magnitude codes used in isolation can trigger the activation of spatial codes. Thus, spatial and numerical codes must be used jointly to evoke spatially organised mental number lines.

neuroscience↗

bioRxiv2018

Feature-specific prediction errors for visual mismatch support predictive coding accounts of perception

Predictive coding (PC) theory posits that our brain employs a predictive model of the environment to infer the causes of its sensory inputs. A fundamental but untested prediction of this theory is that the same stimulus should elicit distinct precision weighted prediction errors (pwPEs) when different (feature-specific) predictions are violated, even in the absence of attention. Here, we tested this hypothesis using functional magnetic resonance imaging (fMRI) and a multi-feature roving visual mismatch paradigm where rare changes in either color (red, green), or emotional expression (happy, fearful) of faces elicited pwPE responses in human participants. Using a computational model for learning and inference, we simulated pwPE trajectories of a Bayes-optimal observer and used these to analyze changes in blood oxygen level dependent (BOLD) responses to changes in color and emotional expression of faces while participants engaged in a distractor task. Controlling for visual attention by eye-tracking, we found pwPE responses to unexpected color changes in the fusiform gyrus. Conversely, unexpected changes of facial emotions elicited pwPE responses in thalamo-cortico-cerebellar structures associated with emotion processing. Our results support a general role of PC across perception, from low-level to complex and socially relevant object features, and suggest that monitoring of the social environment occurs continuously and automatically, even in the absence of attention.\n\nHighlightsPredictive coding (PC) implies that brain responses should reflect transient precision weighted prediction errors (pwPEs). By using fMRI we show that rare changes in color or emotional expression of human faces elicit pwPE responses in dedicated neuronal circuits with known specialization in processing color and emotion-related information, respectively. Our results demonstrate that physically identical stimuli elicit pwPEs in distinct neuronal circuits when different (feature-specific) predictions are violated, depending on current sensory expectations based on prior stimulus context. The demonstration of pwPEs in visual areas as well as in emotion processing structures lends experimental support to theoretical accounts of PC in color and social perception, respectively.

neuroscience↗

bioRxiv2018

A comprehensive framework to capture the arcana of neuroimaging analysis

Mastering the \"arcana of neuroimaging analysis\", the obscure knowledge required to apply an appropriate combination of software tools and parameters to analyse a given neuroimaging dataset, is a time consuming process. Therefore, it is not typically feasible to invest the additional effort required generalise workflow implementations to accommodate for the various acquisition parameters, data storage conventions and computing environments in use at different research sites, limiting the reusability of published workflows.\n\nWe present a novel software framework, Abstraction of Repository-Centric ANAlysis (Arcana), which enables the development of complex, \"end-to-end\" workflows that are adaptable to new analyses and portable to a wide range of computing infrastructures. Analysis templates for specific image types (e.g. MRI contrast) are implemented as Python classes, which define a range of potential derivatives and analysis methods. Arcana retrieves data from imaging repositories, which can be BIDS datasets, XNAT instances or plain directories, and stores selected derivatives and associated provenance back into a repository for reuse by subsequent analyses. Workflows are constructed using Nipype and can be executed on local workstations or in high performance computing environments. Generic analysis methods can be consolidated within common base classes to facilitate code-reuse and collaborative development, which can be specialised for study-specific requirements via class inheritance. Arcana provides a framework in which to develop unified neuroimaging workflows that can be reused across a wide range of research studies and sites.

bioinformatics↗

bioRxiv2018

Child Growth Predicts Brain Functional Connectivity and Future Cognitive Outcomes in Urban Bangladeshi Children Exposed to Early Adversities

BackgroundFaltered growth has been shown to affect 161 million children worldwide and derail cognitive development from early childhood. The neural pathways by which growth faltering in early childhood affects future cognitive outcomes remain unclear, which is partially due to the scarcity of research using both neuroimaging and sensitive behavioral techniques in low-income settings. We employed EEG to examine the association between growth faltering and brain functional connectivity and whether brain functional connectivity mediates the effect of early adversity on cognitive development.\n\nMethodsWe recruited participants from an urban impoverished neighborhood in Dhaka, Bangladesh. One sample consisted of 85 children whose EEG and growth measures (height for age, weight for age, and weight to height) were collected at 6 months and cognitive outcomes were assessed at 27 months. Another sample consisted of 115 children whose EEG and growth measures were collected at 36 months and IQ scores were assessed at 48 months. Path analysis was used to test the effect of growth measures on cognitive outcomes through brain functional connectivity.\n\nFindingsFaltered growth was found to be accompanied by overall increased functional connectivity in the theta and low-beta frequency bands for the 36-month-old cohort. For both cohorts, brain functional connectivity was negatively predictive of later cognitive outcomes at 27 and 48 months, respectively. Faltered growth was found to have a negative impact on childrens IQ scores in the older cohort, and this effect was found to be mediated by brain functional connectivity in the low-beta band.\n\nInterpretationThe association found between growth measures and brain functional connectivity may reflect a broad deleterious effect of malnutrition on childrens brain development. The mediation effect of functional connectivity on the relation between physical growth and later IQ scores provides the first experimental evidence that brain functional connectivity may mediate the effect of biological adversity on cognitive development.\n\nFundingBill and Melinda Gates Foundation (OPP1111625)

neuroscience↗

bioRxiv2018

LRRK2 exonic variants associated with Parkinson’s disease augment phosphorylation levels for LRRK2-Ser1292 and Rab10-Thr73

Leucine-rich repeat kinase 2 (LRRK2) is associated to Parkinsons disease (PD). The most common form of LRRK2 PD is caused by the G2019S variant. Besides G2019S, eight other LRRK2 variants causing familial PD also have amino acid substitutions located in a LRRK2 enzymatic domainsuggesting that enzymatic activity is at the core of mechanisms underlying disease risk. Common LRRK2 polymorphic risk variations such as G2385R, A419V, R1628 and M1646T all reside in other LRRK2 domains. Prior knowledge is limited on how these variants influence LRRK2 function. To investigate the impact on enzymatic function of both rare and common LRRK2 variation a comprehensive profiling of nineteen LRRK2 exonic variants was pursued. Six LRRK2 phosphorylation sites were identified by mass spectrometry. Besides already known phosphorylation sites such as Ser910, Ser935, Ser955, Ser973 and Ser1292 also Thr826 was confirmed by a targeted MRM assay as a LRRK2 phosphorylation site in mammalian cells. Phosphorylation site occupancy for all six LRRK2 sites was obtained but no obvious correlation to risk of disease was found. Instead, application of phospho-specific antibodies targeting LRRK2 phosphorylation sites confirmed that autophosphorylation at Ser1292 was significantly increased for all disease-causing variants whereas no significant differences could be observed for the common intermediate risk variants. Recently, Rab10 and Rab12 have been shown to be bona fide LRRK2 substrates and we find that both rare and common LRRK2 exonic variants augment the phosphorylation of Rab10. This was not observed with Rab12. Furthermore, the protective variant N551K has reduced Rab10 phosphorylation compared to LRRK2 WT. This was not observed with the protective variant R1398H. Our findings support the hypothesis that increased LRRK2 kinase function is associated with increased PD risk but also highlights the need for more sensitive tools for detection of increases in kinase activity in carriers of LRRK2 PD risk variants.\n\nAbbreviations

biochemistry↗

bioRxiv2018

Phoneme-level processing in low-frequency cortical responses to speech explained by acoustic features

When we listen to speech, we have to make sense of a waveform of sound pressure. Hierarchical models of speech perception assume that before giving rise to its final semantic meaning, the signal is transformed into unknown intermediate neuronal representations. Classically, studies of such intermediate representations are guided by linguistically defined concepts such as phonemes. Here we argue that in order to arrive at an unbiased understanding of the mechanisms of speech comprehension, the focus should instead lie on representations obtained directly from the stimulus. We illustrate our view with a strongly data-driven analysis of a dataset of 24 young, healthy humans who listened to a narrative of one hour duration while their magnetoencephalogram (MEG) was recorded. We find that two recent results, a performance gain of an encoding model based on acoustic and annotated linguistic features over a model based on acoustic features alone as well as the decoding of subgroups of phonemes from phoneme-locked responses, can be explained with an encoding model entirely based on acoustic features. These acoustic features capitalise on acoustic edges and outperform Gabor-filtered spectrograms, features with the potential to describe the spectrotemporal characteristics of individual phonemes. We conclude that models of brain responses based on linguistic features can serve as excellent benchmarks. However, we put forward that linguistic concepts are better used when interpreting models, not when building them. In doing so, we find that the results of our analyses favour syllables over phonemes as candidate intermediate speech representations visible with fast non-invasive neuroimaging.

neuroscience↗

bioRxiv2018

Interplay between consensus and divergent RNA polymerase II C-terminal domain repeats in viability and targeting

The carboxy-terminal domain (CTD) of RNA polymerase II (Pol II) is composed of repeats of the consensus YSPTSPS, and is an essential binding scaffold for transcription-associated factors. Metazoan CTDs have well-conserved lengths and sequence compositions arising from the evolution of divergent motifs, features thought to be essential for development. To the contrary, we show that a truncated CTD composed solely of YSPTSPS repeats fully supports Drosophila viability, but a CTD with enough YSPTSPS repeats to match the length of the wild-type Drosophila CTD is defective. Furthermore, a fluorescently-tagged CTD lacking the rest of Pol II dynamically enters transcription compartments, indicating that the CTD functions as a signal sequence. However, CTDs with too many YSPTSPS repeats are more prone to localize to static nuclear foci independent of the chromosomes. We propose that the sequence complexity of the CTD offsets aberrant behavior caused by excessive repetitive sequences without compromising its targeting function.

molecular biology↗

bioRxiv2018

Developmental and conditional dynamics of gene expression in single root cells of A. thaliana

Single-cell RNA-seq can yield high-resolution cell-type-specific expression signatures that reveal new cell types and the developmental trajectories of cell lineages. Here, we apply this approach to A. thaliana root cells to capture gene expression in 3,121 root cells. We analyze these data with Monocle 3, which orders single cell transcriptomes in an unsupervised manner and uses machine learning to reconstruct single-cell developmental trajectories along pseudotime. We identify hundreds of genes with cell-type-specific expression, with pseudotime analysis of several cell lineages revealing both known and novel genes that are expressed along a developmental trajectory. We identify transcription factor motifs that are enriched in early and late cells, together with the corresponding candidate transcription factors that likely drive the observed expression patterns. We assess and interpret changes in total RNA expression along developmental trajectories and show that trajectory branch points mark developmental decisions. Finally, by applying heat stress to whole seedlings, we address the longstanding question of possible heterogeneity among cell types in the response to an abiotic stress. Although the response of canonical heat shock genes dominates expression across cell types, subtle but significant differences in other genes can be detected among cell types. Taken together, our results demonstrate that single-cell transcriptomics holds promise for studying plant development and plant physiology with unprecedented resolution.

genetics↗