Temporal Identity Research Articles

Dynamic Hippo pathway activity underlies mesenchymal differentiation during lung alveolar morphogenesis.

Alveologenesis, the final stage in lung development, substantially remodels the distal lung, expanding the alveolar surface area for efficient gas exchange. Secondary crest myofibroblasts (SCMF) exist transiently in the neonatal distal lung and are crucial for alveologenesis. However, the pathways that regulate SCMF function, proliferation and temporal identity remain poorly understood. To address this, we purified SCMFs from reporter mice, performed bulk RNA-seq and found dynamic changes in Hippo-signaling components during alveologenesis. We deleted the Hippo effectors Yap/Taz from Acta2-expressing cells at the onset of alveologenesis, causing a significant arrest in alveolar development. Using single cell RNA-seq, we identified a distinct cluster of cells in mutant lungs with altered expression of marker genes associated with proximal mesenchymal cell types, airway smooth muscle and alveolar duct myofibroblasts. In vitro studies confirmed that Yap/Taz regulates myofibroblast-associated gene signature and contractility. Together, our findings show that Yap/Taz is essential for maintaining functional myofibroblast identity during postnatal alveologenesis.

Parkinson’s disease and schizophrenia interactomes contain temporally distinct gene clusters underlying comorbid mechanisms and unique disease processes

Genome-wide association studies suggest significant overlaps in Parkinson’s disease (PD) and schizophrenia (SZ) risks, but the underlying mechanisms remain elusive. The protein-protein interaction network (‘interactome’) plays a crucial role in PD and SZ and can incorporate their spatiotemporal specificities. Therefore, to study the linked biology of PD and SZ, we compiled PD- and SZ-associated genes from the DisGeNET database, and constructed their interactomes using BioGRID and HPRD. We examined the interactomes using clustering and enrichment analyses, in conjunction with the transcriptomic data of 26 brain regions spanning foetal stages to adulthood available in the BrainSpan Atlas. PD and SZ interactomes formed four gene clusters with distinct temporal identities (Disease Gene Networks or ‘DGNs’1-4). DGN1 had unique SZ interactome genes highly expressed across developmental stages, corresponding to a neurodevelopmental SZ subtype. DGN2, containing unique SZ interactome genes expressed from early infancy to adulthood, correlated with an inflammation-driven SZ subtype and adult SZ risk. DGN3 contained unique PD interactome genes expressed in late infancy, early and late childhood, and adulthood, and involved in mitochondrial pathways. DGN4, containing prenatally-expressed genes common to both the interactomes, involved in stem cell pluripotency and overlapping with the interactome of 22q11 deletion syndrome (comorbid psychosis and Parkinsonism), potentially regulates neurodevelopmental mechanisms in PD-SZ comorbidity. Our findings suggest that disrupted neurodevelopment (regulated by DGN4) could expose risk windows in PD and SZ, later elevating disease risk through inflammation (DGN2). Alternatively, variant clustering in DGNs may produce disease subtypes, e.g., PD-SZ comorbidity with DGN4, and early/late-onset SZ with DGN1/DGN2.

Ripening dynamics revisited: an automated method to track the development of asynchronous berries on time-lapse images

BackgroundGrapevine berries undergo asynchronous growth and ripening dynamics within the same bunch. Due to the lack of efficient methods to perform sequential non-destructive measurements on a representative number of individual berries, the genetic and environmental origins of this heterogeneity, remain nearly unknown. To address these limitations, we propose a method to track the growth and coloration kinetics of individual berries on time-lapse images of grapevine bunches.ResultsFirst, a deep-learning approach is used to detect berries with at least 50 ± 10% of visible contours, and infer the shape they would have in the absence of occlusions. Second, a tracking algorithm was developed to assign a common label to shapes representing the same berry along the time-series. Training and validation of the methods were performed on challenging image datasets acquired in a robotised high-throughput phenotyping platform. Berries were detected on various genotypes with a F1-score of 91.8%, and segmented with a mean absolute error of 4.1% on their area. Tracking allowed to label and retrieve the temporal identity of more than half of the segmented berries, with an accuracy of 98.1%. This method was used to extract individual growth and colour kinetics of various berries from the same bunch, allowing us to propose the first statistically relevant analysis of berry ripening kinetics, with a time resolution lower than one day.ConclusionsWe successfully developed a fully-automated open-source method to detect, segment and track overlapping berries in time-series of grapevine bunch images acquired in laboratory conditions. This makes it possible to quantify fine aspects of individual berry development, and to characterise the asynchrony within the bunch. The interest of such analysis was illustrated here for one cultivar, but the method has the potential to be applied in a high throughput phenotyping context. This opens the way for revisiting the genetic and environmental variations of the ripening dynamics. Such variations could be considered both from the point of view of fruit development and the phenological structure of the population, which would constitute a paradigm shift.

The Crisis of Legitimacy

ABSTRACT In recent years, the West has increasingly experienced a sense that the political aspects of its social life have undergone a profound alteration. There is a sense of blockage, of non-responsiveness, a feeling that the political class no longer represents the interests of the broader society. Underlying all of this is a loss of legitimacy. What exactly is legitimacy? How does it function? How is it lost? These are the questions that I address in this article. While I refer to Max Weber’s remarks on legitimacy, my thesis is my own. My claim is that legitimacy involves temporal identity. It depends upon the ability of both individuals and peoples to identify themselves as the same over time. Legitimacy’s breakdown is the breakdown of this identity.

In This Issue

The sequential production of cell types during neural development is controlled by temporal identity transcription factors, and heterochronic expression of these factors in progenitors reprograms developmental potential and promotes the ...Temporal identity factors are sufficient to reprogram developmental competence of neural progenitors and shift cell fate output, but whether they can also reprogram the identity of terminally differentiated cells is unknown. To address this question, we ...

Direct neuronal reprogramming by temporal identity factors

Temporal identity factors are sufficient to reprogram developmental competence of neural progenitors and shift cell fate output, but whether they can also reprogram the identity of terminally differentiated cells is unknown. To address this question, we designed a conditional gene expression system that allows rapid screening of potential reprogramming factors in mouse retinal glial cells combined with genetic lineage tracing. Using this assay, we found that coexpression of the early temporal identity transcription factors Ikzf1 and Ikzf4 is sufficient to directly convert Müller glial (MG) cells into cells that translocate to the outer nuclear layer (ONL), where photoreceptor cells normally reside. We name these "induced ONL (iONL)" cells. Using genetic lineage tracing, histological, immunohistochemical, and single-cell transcriptome and multiome analyses, we show that expression of Ikzf1/4 in MG invivo, without retinal injury, mostly generates iONL cells that share molecular characteristics with bipolar cells, although a fraction of them stain for Rxrg, a cone photoreceptor marker. Furthermore, we show that coexpression of Ikzf1 and Ikzf4 can reprogram mouse embryonic fibroblasts to induced neurons in culture by rapidly remodeling chromatin and activating a neuronal gene expression program. This work uncovers general neuronal reprogramming properties for temporal identity factors in terminally differentiated cells.

Antagonistic role of the BTB-zinc finger transcription factors Chinmo and Broad-Complex in the juvenile/pupal transition and in growth control.

During development, the growing organism transits through a series of temporally regulated morphological stages to generate the adult form. In humans, for example, development progresses from childhood through to puberty and then to adulthood, when sexual maturity is attained. Similarly, in holometabolous insects, immature juveniles transit to the adult form through an intermediate pupal stage when larval tissues are eliminated and the imaginal progenitor cells form the adult structures. The identity of the larval, pupal, and adult stages depends on the sequential expression of the transcription factors chinmo, Br-C, and E93. However, how these transcription factors determine temporal identity in developing tissues is poorly understood. Here, we report on the role of the larval specifier chinmo in larval and adult progenitor cells during fly development. Interestingly, chinmo promotes growth in larval and imaginal tissues in a Br-C-independent and -dependent manner, respectively. In addition, we found that the absence of chinmo during metamorphosis is critical for proper adult differentiation. Importantly, we also provide evidence that, in contrast to the well-known role of chinmo as a pro-oncogene, Br-C and E93 act as tumour suppressors. Finally, we reveal that the function of chinmo as a juvenile specifier is conserved in hemimetabolous insects as its homolog has a similar role in Blatella germanica. Taken together, our results suggest that the sequential expression of the transcription factors Chinmo, Br-C and E93 during larva, pupa an adult respectively, coordinate the formation of the different organs that constitute the adult organism.

Child naming and the need for cultural decolonization initiatives Among the Hausa in Northern Nigeria

This paper revisits the naming practices among cultures and peoples across Northern Nigeria, especially the Hausa, in relation to the question of cultural coloniality and the need for decolonial initiatives that can reposition value systems being buried by colonial power relations. Naming, prior to the Arab presence or Arab colonization in the region, was a space that foregrounds the history, spatial and temporal identities of the person bearing the name. It also occasioned people’s expectations and hopes on the child who was given the name. There was no arbitrariness in this knowledge-based system of naming. However, with the advent of Islam and its attendant Arab culture from the 7th to the eleventh and twelfth century, people’s cultural practices, especially in the naming spaces, became increasingly hybridized to contain Arabic influences. Arabic names have now dominated the naming spaces throughout the region, especially among the Hausa-Muslim families. The increasing influence of Western culture does not alter this practice. It intensifies the urge to identify and sound Arab, to Arabize by going beyond the names of pious figures found in Islam. Naming today in the region is informed by the fancies of Arab sounding names that are often unconnected to people’s realities, identities, and personal and collective histories. These names are typical among educated middle class. They range from names of animals to places and objects. This paper digs out the meanings of names given to people before the arrival of Arabic culture in Northern Nigeria as part of indigenous epistemologies that are becoming unpopular because of the pejorative notions associated with them today as animist practices. It also portrays some popular Arabic names and their meanings that are prioritized today. It foregrounds the conceptualization of identities in the Hausa language, the lingua-franca of the greater part of Northern Nigeria.

Jarid2 promotes temporal progression of retinal progenitors via repression of Foxp1

Transitions in competence underlie the ability of CNS progenitors to generate a diversity of neurons and glia. Retinal progenitor cells in mouse generate early-born cell types embryonically and late-born cell types largely postnatally. We find that the transition from early to late progenitor competence is regulated by Jarid2. Loss of Jarid2 results in extended production of early cell types and extended expression of early progenitor genes. Jarid2 can regulate histone modifications, and we find reduction of repressive mark H3K27me3 on a subset of early progenitor genes with loss of Jarid2, most notably Foxp1. We show that Foxp1 regulates the competence to generate early-born retinal cell types, promotes early and represses late progenitor gene expression, and is required for extending early retinal cell production after loss of Jarid2. We conclude that Jarid2 facilitates progression of retinal progenitor temporal identity by repressing Foxp1, which is a primary regulator of early temporal patterning.

Confronting the Contested Past: Sensemaking and Rhetorical History in the Reconstruction of Organizational Identity

This study explores how organizations experience and respond to identity challenges that arise due to conflicting interpretations of their past. Drawing on a case study of a fintech venture, we offer a process model that illuminates the unfolding of “temporal identity complexity,” a sensemaking process that involves different members developing conflicting understandings of how the past undermines the organizational identity. Our model also reveals how leaders can restore members’ beliefs in the organizational identity through “temporal synergizing,” a sensegiving process that recombines conflicting interpretations of the past to support desired identity claims in the present and future. In contrast with prior research that emphasizes the need to construe a sense of identity continuity over time, we show how organizations can instead capitalize on perceived discontinuity in their past to reaffirm identity. We discuss this and other contributions to research on organizational identity, focusing on its threads on sensemaking and rhetorical history. This includes exploring the important role that temporality and emotions play in organizational identity reconstruction.

Ikaros family proteins redundantly regulate temporal patterning in the developing mouse retina.

Temporal identity factors regulate competence of neural progenitors to generate specific cell types in a time-dependent manner, but how they operate remains poorly defined. In the developing mouse retina, the Ikaros zinc-finger transcription factor Ikzf1 regulates production of early-born cell types, except cone photoreceptors. In this study we show that, during early stages of retinal development, another Ikaros family protein, Ikzf4, functions redundantly with Ikzf1 to regulate cone photoreceptor production. Using CUT&RUN and functional assays, we show that Ikzf4 binds and represses genes involved in late-born rod photoreceptor specification, hence favoring cone production. At late stages, when Ikzf1 is no longer expressed in progenitors, we show that Ikzf4 re-localizes to target genes involved in gliogenesis and is required for Müller glia production. We report that Ikzf4 regulates Notch signaling genes and is sufficient to activate the Hes1 promoter through two Ikzf GGAA-binding motifs, suggesting a mechanism by which Ikzf4 may influence gliogenesis. These results uncover a combinatorial role for Ikaros family members during nervous system development and provide mechanistic insights on how they temporally regulate cell fate output.

Inference-Domain Network Evolution: A New Perspective for One-Shot Multi-Object Tracking.

The supervised one-shot multi-object tracking (MOT) algorithms have achieved satisfactory performance benefiting from a large amount of labeled data. However, in real applications, acquiring plenty of laborious manual annotations is not practical. It is necessary to adapt the one-shot MOT model trained on a labeled domain to an unlabeled domain, yet such domain adaptation is a challenging problem. The main reason is that it has to detect and associate multiple moving objects distributed in various spatial locations, but there are obvious discrepancies in style, object identity, quantity, and scale among different domains. Motivated by this, we propose a novel inference-domain network evolution to enhance the generalization ability of the one-shot MOT model. Specifically, we design a spatial topology-based one-shot network (STONet) to perform the one-shot MOT task, where a self-supervision mechanism is employed to stimulate the feature extractor to learn the spatial contexts without any annotated information. Furthermore, a temporal identity aggregation (TIA) module is proposed to assist STONet to weaken the adverse effects of noisy labels in the network evolution. This designed TIA aggregates historical embeddings with the same identity to learn cleaner and more reliable pseudo labels. In the inference domain, the proposed STONet with TIA performs pseudo label collection and parameter update progressively to realize the network evolution from the labeled source domain to an unlabeled inference domain. Extensive experiments and ablation studies conducted on MOT15, MOT17, and MOT20, demonstrate the effectiveness of our proposed model.

A Self-Adaptive Temporal-Spatial Self-Training Algorithm for Semisupervised Fault Diagnosis of Industrial Processes

Investigating process monitoring techniques is required to reduce the loss of property and life caused by industrial processes accidents. Fault diagnosis, which attempts to determine the fault type, is a vital step in process monitoring because it can help operators respond to abnormal situations appropriately. Adequate data labels to train supervised fault diagnosis models are difficult to acquire in practice; however, semisupervised methods, which are attracting increasing attention, can use unlabeled data. Self-labeled algorithms are an effective paradigm of semisupervised methods, but their applications in industrial process fault diagnosis do not meet expectations, because they are prone to performance deterioration when handling industrial process data. To address this issue, in this article, a self-training algorithm with a modified confidence measure is proposed. The confidence measure is temporal-spatial with temporal identities of data introduced to its definition and calculation, which makes the algorithm adaptable to industrial processes. The proposed algorithm is also self-adaptive to avoid time-consuming hyperparameter tuning processes. The benchmark Tennessee Eastman process data were used to evaluate the proposed algorithm, and the experiment results demonstrate its superiority compared to competing semisupervised methods.

Entanglement in Time: Nostalgic Affect as Cine-Choreography in The White Crow (2018) and Suspiria (2018)

This essay is an investigation into the historical claim of a work of screendance that involves re-imagination, re-composition, or re-enactment: In what way does it access history? And how should we treat, with due seriousness, the vicarious aura of historicity these works afford? After identifying the ontological status of time as the blind spot in the debate regarding the corporeal relationship to the archive, I introduce the Deleuzian conception of time as an incessant exchange between the virtual and the actual. I present the hauntology of certain pasts as a result of the virtual-actual exchange dissipating the temporal identity of an event, which is in turn experienced as the subject's dispersion of the self. And I redefine the body as a corporeal-archival system that channels the exchange. I then analyze the nostalgic tones of the two selected films as affects formulated by cine-choreographies that express the dispersion of the self as an experience of the dissipation of the temporal identity of an event, thereby providing an analytical approach that makes it possible to interpret such screendance practices' claim to history.

The Drosophila homologue of CTIP1 (Bcl11a) and CTIP2 (Bcl11b) regulates neural stem cell temporal patterning.

ABSTRACTIn the developing nervous system, neural stem cells (NSCs) use temporal patterning to generate a wide variety of different neuronal subtypes. In Drosophila, the temporal transcription factors, Hunchback, Kruppel, Pdm and Castor, are sequentially expressed by NSCs to regulate temporal identity during neurogenesis. Here, we identify a new temporal transcription factor that regulates the transition from the Pdm to Castor temporal windows. This factor, which we call Chronophage (or ‘time-eater’), is homologous to mammalian CTIP1 (Bcl11a) and CTIP2 (Bcl11b). We show that Chronophage binds upstream of the castor gene and regulates its expression. Consistent with Chronophage promoting a temporal switch, chronophage mutants generate an excess of Pdm-specified neurons and are delayed in generating neurons associated with the Castor temporal window. In addition to promoting the Pdm to Castor transition, Chronophage also represses the production of neurons generated during the earlier Hunchback and Kruppel temporal windows. Genetic interactions with Hunchback and Kruppel indicate that Chronophage regulates NSC competence to generate Hunchback- and Kruppel-specified neurons. Taken together, our results suggest that Chronophage has a conserved role in temporal patterning and neuronal subtype specification.

Navigating Cultural Divides via Identity Work: Bulgarian Migrant Entrepreneurs’ Tactics in the UK

ABSTRACTThe changing geopolitical landscapes and increased migration flow across the world call for a fresh perspective on the sociocultural and economic integration of migrants in their new ‘homes’ and ‘communities’. In this qualitative process study, we provide insight into the identity work dynamics that underlie interfirm cooperation in the new business context. We see a sample of Bulgarian migrant entrepreneurs as knowledge boundary spanners who employ identity work tactics for the development of shared norms and values that facilitate knowledge exchange between their home culture and the UK host culture context. This study suggests that knowledge boundary spanning is enabled by a temporal identity work process, characterized by a series of inward and outward identity work tactics. The interplay between inward and outward identity work tactics occurs over phases of identifying identity differences, adopting identity cues, and finally, realizing hybrid identity. This article contributes to the identity work and migrant entrepreneurship literature by exploring the underlying mechanisms for realizing knowledge boundary spanning by migrant entrepreneurs.

Impaired Cell Cycle Progression and Self-Renewal of Fetal Neural Stem and Progenitor Cells in a Murine Model of Intrauterine Growth Restriction

Individuals with intrauterine growth restriction (IUGR) are at an increased risk for neurodevelopmental impairment. Fetal cortical neurogenesis is a time-sensitive process in which fetal neural stem cells (NSCs) follow a distinct pattern of layer-specific neuron generation to populate the cerebral cortex. Here, we used a murine maternal hypoxia-induced IUGR model to study the impact of IUGR on fetal NSC development. In this model, timed-pregnant mice were exposed to hypoxia during the active stage of neurogenesis, followed by fetal brain collection and analysis. In the IUGR fetal brains, we found a significant reduction in cerebral cortical thickness accompanied by decreases in layer-specific neurons. Using EdU labeling, we demonstrated that cell cycle progression of fetal NSCs was delayed, primarily observed in the G2/M phase during inward interkinetic nuclear migration. Following relief from maternal hypoxia exposure, the remaining fetal NSCs re-established their neurogenic ability and resumed production of layer-specific neurons. Surprisingly, the newly generated neurons matched their control counterparts in layer-specific marker expression, suggesting preservation of the fetal NSC temporal identity despite IUGR effects. As expected, the absolute number of neurons generated in the IUGR group remained lower compared to that in the control group due to a reduced fetal NSC pool size as a result of cell cycle defect. Transcriptome analysis identified genes related to energy expenditure and G2/M cell cycle progression being affected by maternal hypoxia-induced IUGR. Taken together, maternal hypoxia-induced IUGR is associated with a defect in cell cycle progression of fetal NSCs, and has a long-term impact on offspring cognitive development.

Transcriptional profiling from whole embryos to single neuroblast lineages in Drosophila

Embryonic development results in the production of distinct tissue types, and different cell types within each tissue. A major goal of developmental biology is to uncover the “parts list” of cell types that comprise each organ. Here we perform single cell RNA sequencing (scRNA-seq) of the Drosophila embryo to identify the genes that characterize different cell and tissue types during development. We assay three different timepoints, revealing a coordinated change in gene expression within each tissue. Interestingly, we find that the elav and Mhc genes, whose protein products are widely used as markers for neurons and muscles, respectively, show broad pan-embryonic expression, indicating the importance of post-transcriptional regulation. We next focus on the central nervous system (CNS), where we identify genes whose expression is enriched at each stage of neuronal differentiation: from neural progenitors, called neuroblasts, to their immediate progeny ganglion mother cells (GMCs), followed by new-born neurons, young neurons, and the most mature neurons. Finally, we ask whether the clonal progeny of a single neuroblast (NB7-1) share a similar transcriptional identity. Surprisingly, we find that clonal identity does not lead to transcriptional clustering, showing that neurons within a lineage are diverse, and that neurons with a similar transcriptional profile (e.g. motor neurons, glia) are distributed among multiple neuroblast lineages. Although each lineage consists of diverse progeny, we were able to identify a previously uncharacterized gene, Fer3, as an excellent marker for the NB7-1 lineage. Within the NB7-1 lineage, neurons which share a temporal identity (e.g. Hunchback, Kruppel, Pdm, and Castor temporal transcription factors in the NB7-1 lineage) have shared transcriptional features, allowing for the identification of candidate novel temporal factors or targets of the temporal transcription factors. In conclusion, we have characterized the embryonic transcriptome for all major tissue types and for three stages of development, as well as the first transcriptomic analysis of a single, identified neuroblast lineage, finding a lineage-enriched transcription factor.

Regulation of developmental hierarchy in Drosophila neural stem cell tumors by COMPASS and Polycomb complexes.

COMPASS and Polycomb complexes are antagonistic chromatin complexes that are frequently inactivated in cancers, but how these events affect the cellular hierarchy, composition, and growth of tumors is unclear. These characteristics can be systematically investigated in Drosophila neuroblast tumors in which cooption of temporal patterning induces a developmental hierarchy that confers cancer stem cell (CSC) properties to a subset of neuroblasts retaining an early larval temporal identity. Here, using single-cell transcriptomics, we reveal that the trithorax/MLL1/2-COMPASS–like complex guides the developmental trajectory at the top of the tumor hierarchy. Consequently, trithorax knockdown drives larval-to-embryonic temporal reversion and the marked expansion of CSCs that remain locked in a spectrum of early temporal states. Unexpectedly, this phenotype is amplified by concomitant inactivation of Polycomb repressive complex 2 genes, unleashing tumor growth. This study illustrates how inactivation of specific COMPASS and Polycomb complexes cooperates to impair tumor hierarchies, inducing CSC plasticity, heterogeneity, and expansion.

Occupational and Sociocultural Temporal Identity Integration: Links to Overall Health for Muslim-Heritage Immigrants to the United States

This study examines the association between temporal identity integration, or how identity is integrated across time, and perceived health for new Muslim immigrants to the United States using the publicly available New Immigrant Survey. We examined the content of identity in the occupational and sociocultural domains. These two content areas are important aspects of the immigration transition and are influenced by the context of Islamophobia. We examined the association of changes across the occupational and sociocultural domains from pre-to-post immigration with four different indicators of health (e.g., current health, change in health, emotional health, and physical health) for 444 Muslim-heritage immigrants. Findings suggest overall perceived health of new Muslim immigrants was good. Hypotheses were partially supported where results suggest small, yet significant, associations between changes in occupational status, English use, and similarity of diet with health indicators. The results emphasize the need to further explore other constructs that are relevant to health for Muslim immigrants in a post-9/11 era.