Biology subjects

Hansen, M.

Publications and source records attributed to Hansen, M..

At least 19 recordsLinked to original sources

bioRxiv2026

Autophagy activator AA-20 engages CDK5 to promote lipophagy and improve neurodegeneration-associated phenotypes

Lipophagy, the selective degradation of lipid droplets (LDs) by autophagy, has the potential to ameliorate neurodegenerative diseases such as Parkinson's (PD) and Alzheimer's (AD), wherein LD accumulation has been linked to the exacerbation of the proteinopathy component of neurodegeneration. Pharmacological lipophagy inducers remain scarce. We previously identified AA-20 as a novel autophagy activator that acts independently of mTORC1 inhibition, thereby providing a means of stimulating autophagy while avoiding the immunosuppressive side effects associated with direct mTORC1 inhibition. Prior work also showed that AA-20 treatment reduces PolyQ aggregate levels in several C. elegans tissues. Here, we demonstrate that AA-20 enhances LD recruitment to autophagosomes and promotes LD degradation via lysosomal acid lipase activation in murine hippocampal neuronal cells, consistent with lipophagy activation. In human Swedish Amyloid Precursor Protein mutated cerebral organoids, two weeks of AA-20 treatment normalized aberrant lipidomic profiles by selectively reducing various disease-associated lipids, while also correcting the AD-associated electrical hyperexcitability phenotype. Moreover, we identified cyclin-dependent kinase 5 (CDK5), a neuronal kinase linked to AD hyperexcitability and PD pathology, as a target of AA-20. AA-20-induced autophagy and lipid clearance in HT22 cells require CDK5. In a neuronal seeding model of -synuclein pathology, AA-20 reduced pS129--synuclein levels. Collectively, these findings indicate AA-20 can promote lipophagic clearance of LDs and mitigate multiple cellular phenotypes associated with lipidopathy and proteinopathy in neurodegenerative disease models.

molecular biology↗

bioRxiv2026

The WD40 domain of autophagy protein ATG-16.2 is required for lysosomal regulation and longevity in germline-less C. elegans

Autophagy is a conserved cellular recycling pathway linked to longevity and regulated by autophagy-related (ATG) protein. Many of these proteins serve a key function in ATG8 lipidation onto autophagosomal membranes, a step that precedes subsequent lysosomal degradation. Recently, mammalian ATG16L1, a member of ATG8 lipidation machinery, have been shown to also direct ATG8 lipidation onto other membranes via its C-terminal WD40 domain in acutely stressed cells. However, whether such non-canonical functions of the ATG16L1 WD40 domain influence longevity remain largely unknown. Here, we endogenously deleted the WD40 domain of atg-16.2, the C. elegans ortholog of ATG16L1, and examined autophagy, healthspan and longevity. The ATG-16.2 WD40 domain was dispensable for healthspan measures and for ATG8 lipidation in whole animals and neurons but was required for autophagic flux across all major tissues examined. Notably, the ATG-16.2 WD40 domain was also critical in limiting lysosomal membrane damage after acute heat stress. Because long-lived C. elegans mutants are typically heat resistant, we asked whether this lysosomal function supported their thermotolerance and found the WD40 domain to be selectively required for thermotolerance induced by germline removal, but not by reduced insulin/IGF-1 signaling or dietary restriction. In germline-less animals, loss of the ATG-16.2 WD40 domain reduced nuclear TFEB/HLH-30, reduced neuronal autophagic degradation, altered neuronal lysosomal pH, and sensitized animals to heat-induced lysosomal damage. Collectively, these findings establish the ATG16 WD40 domain as a regulator of autophagic degradation and lysosomal integrity in vivo, and show that this role is associated with longevity in a pathway-selective manner.

genetics↗

bioRxiv2026

Microphysiological Flow Batteries For Dynamic EDC Screening Of mESC-derived Thyroid Organoids

Endocrine disrupting chemicals (EDCs) are ubiquitous environmental contaminants capable of dysregulating the production of thyroid hormones. Traditional thyroid toxicological assays rely on 2D cell cultures and animal models, both of which fail to accurately recapitulate human thyroid physiology and provide limited mechanistic insight into EDC toxicity. To overcome these limitations, we report a novel thyroid-on-chip platform integrating mouse embryonic stem cell-derived thyroid organoids with advanced organ-on-chip (OoC) technology and downstream multi-omics analysis. The platform leverages a reversibly-sealed microphysiological flow battery (MFB) to allow scale up of dynamic organoid culture and controlled chemical exposure while reducing operational complexity. Upon EDC exposure, transcriptomic and proteomic analysis revealed new molecular signatures of thyroid disruption across four different EDC classes, even at very low EDC concentrations (1nM), validating the capacity of this system to mechanistically dissect EDC-induced responses. This represents an integrated platform consists of an advanced physiologically relevant assay framework for next-generation endocrine toxicity testing, bridging the gap between in vitro screening and in vivo thyroid physiology.

bioengineering↗

bioRxiv2026

The tortured past of young polymorphic sex chromosomes revealed through multiple de novo genome assemblies of the mountain pine beetle

Neo-sex chromosomes provide a powerful system for studying the early stages of sex chromosome evolution and the genomic mechanisms that may contribute to reproductive isolation. Using PacBio long-read HiFi sequencing, Hi-C scaffolding, and sex-specific transcriptomic data, we generated six chromosome-level assemblies (male and female from three populations) of the mountain pine beetle (Dendroctonus ponderosae), a species known to harbor three partially reproductively isolated neo-Y haplogroups. These assemblies reveal that the large neo-X and neo-Y chromosomes formed through sequential fusions of the ancestral X with three autosomes, with recombination cessation occurring at [~]8.6, [~]6.3, and [~]4.3 MYA for each event. Comparative analyses show that while neo-X chromosomes remain largely collinear across populations, neo-Ys exhibit dramatic structural divergence, with 900-1,200 inverted segments per haplogroup and only [~]65% of sequence able to be aligned to the neo-X. Repeat analyses demonstrate moderate TE accumulation on the neo-Y, particularly LTR elements, and gene mapping analyses reveal extensive degeneration: [~]62% of neo-Y genes exhibit gene loss, fragmentation, or disruptive mutations. All populations retain a single pseudoautosomal region (PAR), though PAR size and gene content vary due to neo-Y specific rearrangements. Across neo-Ys, 27 genes are uniquely missing in the Western haplogroup, including previously identified candidates implicated in hybrid male sterility. Broader comparisons among neo-Ys show widespread structural variation, population specific patterns of degeneration, and limited gene family expansions. Together, these results provide the first full characterization of neo-sex chromosome evolution in D. ponderosae, revealing rapid, lineage specific neo-Y degeneration and highlighting the potential for sex chromosome divergence to contribute to emerging reproductive incompatibilities within a single species.

genomics↗

bioRxiv2026

Lenacapavir allosterically remodels the HIV-1 capsid

Lenacapavir (LEN) is a highly potent, long-acting HIV-1 capsid inhibitor that holds exceptional promise for pre-exposure prophylaxis. LEN causes the mature viral capsid to rupture and lose integrity, but the underlying mechanism has been unclear. Here, we show that LEN is an allosteric modulator of HIV-1 capsid structure that breaks the capsids fullerene cone architecture in two steps: loss of high-curvature declinations occurs early, followed by failure of the capsid body. At the molecular level, LEN alters the non-covalent bonding interactions between capsid subunits and reduces local lattice curvature. LEN also alters the material properties of the capsid, by increasing brittleness. These results provide molecular rationales for how LEN remodels HIV-1 capsid structure and impairs the replication capacity of the virus.

microbiology↗

bioRxiv2025

Senescent cells secrete chromatin components via senescence-associated extracellular particles

Senescent cells influence their surroundings through the senescence-associated secretory phenotype (SASP), an assortment of secreted molecules and macromolecular complexes. Among SASPs intracellular drivers are cytoplasmic chromatin fragments (CCFs), nuclear-derived DNA that activates the pro-inflammatory cGAS/STING pathway. While autophagy contributes to CCFs degradation, the full repertoire of CCF fates and signaling functions remains unclear. Here, we show that senescent cells release CCF components, {gamma}H2AX and double-stranded DNA (dsDNA), into the extracellular space via an ESCRT-independent multivesicular body pathway. Secreted CCF components localize to extracellular particles exhibiting an unusual "popcorn"-like morphology, distinct from canonical small extracellular vesicles. Notably, inhibition of autophagy enhances secretion of CCF components and particles, suggesting an inverse relationship between intracellular clearance and extracellular release. A fraction of CCF-containing extracellular particles activates cGAS-STING signaling in non-senescent proliferating cells and is enriched in the circulation of aged mice, pointing to a previously unrecognized mode of extracellular signaling by senescent cells.

cell biology↗

bioRxiv2025

NINJ1 is activated by Mycobacterium tuberculosis ESX-1 secreted effector EsxA and mediates necrosis of infected human macrophages

Lytic cell death contributes to tissue damage and dissemination during Mycobacterium tuberculosis (Mtb) infection, yet the mechanisms governing plasma membrane rupture (PMR) remain incompletely defined. Here, we identify Ninjurin-1 (NINJ1), a mediator of PMR, as a central effector of macrophage lysis during Mtb infection. Mtb infection induced NINJ1 oligomerization, and genetic deletion or pharmacological inhibition of NINJ1 markedly reduced lactate dehydrogenase (LDH) release. Cytokine secretion was largely preserved in NINJ1-deficient macrophages, with the exception of CXCL10. Unexpectedly, inhibition of pyroptosis, apoptosis, necroptosis, and ferroptosis - individually or in combination - did not prevent NINJ1 activation or PMR, indicating that Mtb-induced membrane rupture proceeds independently of canonical regulated cell death pathways. However, NINJ1 oligomerization and PMR required the Mtb ESX-1 secretion system, identifying a bacterial virulence determinant as a critical upstream trigger. Although osmoprotective PEG partially reduced LDH release, neither calcium signaling nor cell swelling accounted for NINJ1-dependent PMR in Mtb-infected macrophages. Together, these findings establish NINJ1 as a key executioner of Mtb-induced lytic cell death and reveal an ESX-1-dependent pathway of PMR that is uncoupled from canonical host cell death programs. TeaserNINJ1 mediates plasma membrane rupture of macrophages infected with Mycobacterium tuberculosis

microbiology↗

bioRxiv2025

Host-specific fungal plant pathogens exhibit distinct interactions with the leaf microbiota of wild grasses

The plants microbiome is influenced by the plant species and biotic factors such as the infection by pathogens. Pathogen-microbiome interactions are relevant for the progression of the disease since both can compete within the plant host. We hypothesize that pathogens specialized to different hosts have distinct, direct, and indirect influence on the host microbiome. We focused on the host-specific leaf pathogens Zymoseptoria tritici and Zymoseptoria passerinii. By using microbiome metabarcoding and coculture interactions, we evaluated the influence of virulent (wild host-infecting pathogen) and avirulent (domesticated host-infecting pathogen) Zymoseptoria lineages on the leaf microbiome of the wild grasses Aegilops cylindrica and Hordeum murinum which are hosts to virulent lineages of Z. tritici and Z. passerinii, respectively. Our microbiome analysis showed that the fungal communities were affected by virulent lineages, while the avirulent lineages had the most negative correlations with bacteria. Both virulent and avirulent pathogens had the same spectrum of interactions when experimentally cocultured with bacteria. The intensity of pathogen-induced growth enhancement differed between Zymoseptoria lineages. We demonstrated that sugar metabolism through the fungal secretion of invertase can be a determinant of bacterial growth enhancement. Our study highlights the role of microbial interactions on host-specificity and mechanisms underlying microbial interactions by Zymoseptoria spp.

microbiology↗

bioRxiv2024

Development of antigen-dextramers for detection and evaluation of CAR T cells

BackgroundChimeric antigen receptor (CAR) T cell therapy has transformed the treatment landscape of hematologic cancers by engineering T cells to specifically target and destroy cancer cells. Monitoring CAR T cell activity and function is essential for optimizing therapeutic outcomes, but existing tools for CAR detection are often limited in specificity and functional assessment capability. MethodsWe developed antigen-dextramers by conjugating multiple CAR-specific antigens to a dextran backbone. The dextramers were compared to previously reported antigen-tetramers for their ability to stain and detect CAR T cells. Because these multimers incorporate the CAR target antigen, they uniquely enable assessment of CAR T cell functionality by facilitating binding and activation analyses. We tested the staining and functional properties of the multimers across a range of CAR constructs with different affinities, using flow cytometry, microscopy, and NFAT-luciferase reporter assays. ResultsThe antigen-dextramers demonstrated high specificity and sensitivity in staining CAR T cells, with adjustable antigen density to optimize binding. Antigen-dextramers also enabled effective clustering and subsequent activation of CARs, showing their utility as both a staining and functional assessment tool. The dextramers revealed that CARs with different affinities and clustering tendencies displayed varied binding and activation in response to different antigen densities. ConclusionAntigen-dextramers offer a dual advantage as versatile reagents for both staining and functional analysis of CAR T cells. Their capacity to engage CARs with the specific antigen provides a valuable platform for evaluating CAR functionality, informing CAR design improvements, and enhancing therapeutic precision.

bioengineering↗

bioRxiv2024

Foxi1 regulates multiple steps of mucociliary development and ionocyte specification through transcriptional and epigenetic mechanisms

Foxi1 is a master regulator of ionocytes (ISCs / INCs) across species and organs. Two subtypes of ISCs exist, and both -and {beta}-ISCs regulate pH-and ion-homeostasis in epithelia. Gain and loss of FOXI1 function are associated with human diseases, including Pendred syndrome, male infertility, renal acidosis and cancers. Foxi1 was predominantly studied in the context of ISC specification, however, reports indicate additional functions in early and ectodermal development. Here, we re-investigated the functions of Foxi1 in Xenopus laevis embryonic mucociliary epidermis development and found a novel function for Foxi1 in the generation of Notch-ligand expressing mucociliary multipotent progenitors (MPPs). We demonstrate that Foxi1 has multiple concentration-dependent functions: At low levels, Foxi1 maintains ectodermal competence in MPPs through transcriptional and epigenetic mechanisms, while at high levels, Foxi1 induces a multi-step process of ISC specification and differentiation in cooperation with Ubp1 and Dmrt2. We further describe how foxi1 expression is affected through auto-and Notch-regulation, and how this developmental program affects mucociliary patterning. Together, we reveal novel functions for Foxi1 in Xenopus mucociliary epidermis formation, relevant to our understanding of vertebrate development and human disease.

developmental biology↗

bioRxiv2024

MSA: scalable DNA methylation screening BeadChip for high-throughput trait association studies

Epigenome-wide association studies (EWAS) are transforming our understanding of the interplay between epigenetics and complex human traits and phenotypes. We introduce the Methylation Screening Array (MSA), a new iteration of the Infinium technology for scalable and quantitative screening of trait associations of nuanced ternary-code cytosine modifications in larger, more inclusive, and stratified human populations. MSA integrates EWAS, single-cell, and cell-type-resolved methylome profiles, covering diverse human traits and diseases. Our first MSA applications yield multiple biological insights: we revealed a previously unappreciated role of 5-hydroxymethylcytosine (5hmC) in trait associations and epigenetic clocks. We demonstrated that 5hmCs complement 5-methylcytosines (5mCs) in defining tissues and cells epigenetic identities. In-depth analyses highlighted the cell type context of EWAS and GWAS hits. Using this platform, we conducted a comprehensive human 5hmC aging EWAS, discovering tissue-invariant and tissue-specific aging dynamics, including distinct tissue-specific rates of mitotic hyper- and hypomethylation rates. These findings chart a landscape of the complex interplay of the two forms of cytosine modifications in diverse human tissues and their roles in health and disease.

genomics↗

bioRxiv2024

Temporal dynamics of BMP/Nodal ratio drive tissue-specific gastrulation morphogenesis

Anteroposterior (AP) elongation of the vertebrate body plan is driven by convergence and extension (C&E) gastrulation movements in both the mesoderm and neuroectoderm, but how or whether molecular regulation of C&E differs between tissues remains an open question. Using a zebrafish explant model of AP axis extension, we show that C&E of the neuroectoderm and mesoderm can be uncoupled ex vivo, and that morphogenesis of individual tissues results from distinct morphogen signaling dynamics. Using precise temporal manipulation of BMP and Nodal signaling, we identify a critical developmental window during which high or low BMP/Nodal ratios induce neuroectoderm- or mesoderm-driven C&E, respectively. Increased BMP activity similarly enhances C&E specifically in the ectoderm of intact zebrafish gastrulae, highlighting the in vivo relevance of our findings. Together, these results demonstrate that temporal dynamics of BMP and Nodal morphogen signaling activate distinct morphogenetic programs governing C&E gastrulation movements within individual tissues. SUMMARY STATEMENTUsing zebrafish embryo and explant models, we demonstrate that temporal dynamics of morphogen signaling ratios distinguish between tissue-specific morphogenetic programs during vertebrate body plan formation.

developmental biology↗

bioRxiv2023

Non-target Analysis of Wastewater Treatment Plant Effluents: Chemical Fingerprinting as a Monitoring Tool.

This study aims at discovering and characterizing the plethora of xenobiotic substances released into the environment with wastewater effluents. We present a novel non-targeted screening methodology based on ultra-high resolution Orbitrap mass spectrometry and nanoflow ultra-high performance liquid chromatography together with a new data-processing pipeline. This approach was applied to effluent samples from two state-of-the-art urban, and one small rural wastewater treatment facility. In total, 785 structures were obtained, of these 38 were identified as single compounds, while 480 structures were identified at a putative level. The vast majority of these were therapeutics and drugs, present as parent compounds and metabolites. Using the R packages Phyloseq and MetacodeR, we here present a novel way of visualizing LCMS data while showing significant difference in xenobiotic presence in the wastewater effluents between the three sites. 1. SignificanceWe characterized a wide spectrum of xenobiotic substances using ultra-high performance liquid chromatography, and analysed the data with a new data-processing pipeline using microbial ecological tools to visualize and perform statistical testing of the chemical data to reveal trends in compound composition at the three WWTPs. This approach was applied to obtain and analyse data from effluent samples collected at three wastewater treatment facilities. In total, 785 chemical structures were achieved, with a majority identified as therapeutics and drugs. Several of the compounds are suspected endocrine disruptors. The data reveal a significant difference in compound diversity persisting in the wastewater effluents at the three sites. Our findings reveal the presence of undesirable compounds in effluent released into waterways, and address the greatest challenge in environmental chemistry - pinpointing single compounds of interest from masses of data produced.

ecology↗

bioRxiv2023

Host-gut microbiota interactions shape parasite infections in farmed Atlantic salmon

Animals and their associated microbiota share long evolutionary histories. Both host genotype and associated microbiota influence phenotypes such as growth and disease resilience. We applied a hologenomic approach to explore the relationship between host and microbiota in shaping lifetime growth and parasitic cestode infection in farmed Atlantic salmon. Genomes, transcriptomes, metabolomes and metagenomes were generated from the guts of 460 harvest-aged salmon, 82% of which were naturally infected with an intestinal cestode. One salmonid-specific Mycoplasma dominated the gut microbiota of uninfected salmon. However, the microbiota was perturbed in smaller, parasitised fish, with increased abundance of Vibrionaceae and other Mycoplasma species previously linked to the cestode microbiota. The cestode-associated Mycoplasma carry more virulence-associated genes than the salmonid Mycoplasma. Colonisation by one cestode-associated Mycoplasma was associated with a region of the salmon genome encoding several long noncoding RNA genes previously associated with host control of intestinal microbiota. Integrating the multiple omic datasets revealed coordinated changes in the salmon gut transcriptome and metabolome that correlated with shifts in the microbiota of smaller, parasitised fish. Our results suggest that cestode infections introduce new microbes and trigger host responses, altering the gut microbiota with increases in potentially pathogenic microbes. Establishment of these microbes is partially shaped by the genetic background of the host. Our study highlights the value of a hologenomic approach for gaining an in-depth understanding of trilateral interactions among host, microbiota and parasite.

systems biology↗

bioRxiv2022

Epigenetic reprogramming shapes the cellular landscape of schwannoma

Cell state evolution underlies tumor development and response to therapy1, but mechanisms specifying cancer cell states and intratumor heterogeneity are incompletely understood. Schwannomas are the most common tumors of the peripheral nervous system and are treated with surgery and ionizing radiation2-5. Schwannomas can oscillate in size for many years after radiotherapy6,7, suggesting treatment may reprogram schwannoma cells or the tumor microenvironment. Here we show epigenetic reprogramming shapes the cellular landscape of schwannomas. We find schwannomas are comprised of 2 molecular groups distinguished by reactivation of neural crest development pathways or misactivation of nerve injury mechanisms that specify cancer cell states and the architecture of the tumor immune microenvironment. Schwannoma molecular groups can arise independently, but ionizing radiation is sufficient for epigenetic reprogramming of neural crest to immune-enriched schwannoma by remodeling chromatin accessibility, gene expression, and metabolism to drive schwannoma cell state evolution and immune cell infiltration. To define functional genomic mechanisms underlying epigenetic reprograming of schwannomas, we develop a technique for simultaneous interrogation of chromatin accessibility and gene expression coupled with genetic and therapeutic perturbations in single-nuclei. Our results elucidate a framework for understanding epigenetic drivers of cancer evolution and establish a paradigm of epigenetic reprograming of cancer in response to radiotherapy.

cancer biology↗

bioRxiv2022

Inhibition of early-acting autophagy genes in C. elegans neurons improves protein homeostasis, promotes exopher production, and extends lifespan via the ATG-16.2 WD40 domain

While autophagy is key to maintain cellular homeostasis, tissue-specific roles of individual autophagy genes are less understood. To study neuronal autophagy in vivo, we inhibited autophagy genes specifically in C. elegans neurons, and unexpectedly found that knockdown of early-acting autophagy genes, i.e., involved in formation of the autophagosome, except for atg-16.2, decreased PolyQ aggregates and increased lifespan, albeit independently of the degradation of autophagosomal cargo. Neuronal aggregates can be secreted from neurons via vesicles called exophers, and we found that neuronal inhibition of early-acting autophagy genes atg-7 and lgg-1/Atg8, but not atg-16.2 increased exopher formation. Moreover, atg-16.2 mutants were unable to form exophers, and atg-16.2 was required for the effects of early autophagy gene reduction on neuronal PolyQ aggregation, exopher formation, and lifespan. Notably, neuronal expression of full-length ATG-16.2 but not ATG-16.2 without a functional WD40 domain, important for non-canonical functions of ATG16L1 in mammalian cells, restored these phenotypes. Collectively, we discovered a specific role for C. elegans ATG-16.2 and its WD40 domain in exopher biogenesis, neuronal proteostasis, and lifespan determination, highlighting a possible role for non-canonical autophagy functions in both exopher formation and in aging.

cell biology↗

bioRxiv2022

Relationship between thyroid hormones and associated metabolites and gene expression bioindicators in the serum of Rana catesbeiana tadpoles and frogs during metamorphosis

Anuran metamorphosis is characterized by profound morphological changes including remodeling of tissues and organs. This transition is initiated by thyroid hormones (THs). However, the current knowledge of changing levels of THs during metamorphosis relies on pooled samples using methods known for high variability with sparse reporting of measured variation. Moreover, establishing a clear linkage between key gene expression bioindicators and TH levels throughout the metamorphic process is needed. Using state-of-the-art ultra-high performance liquid chromatography isotope-dilution tandem mass spectrometry, we targeted 12 THs and metabolites in the serum of Rana [Lithobates] catesbeiana (n=5-10) across seven distinct postembryonic stages beginning with premetamorphic tadpoles (Gosner stage 31-33) and continuing through metamorphosis to a juvenile frog (Gosner stage 46). TH levels were related to TH-relevant gene transcripts (thra, thrb, and thibz) in back skin of the same individual animals. Significant increases from basal levels were observed for thyroxine (T4) and 3,3,5-triiodothyronine (T3) at Gosner stage 41, reaching maximal levels at Gosner stage 44 (28{+/-}10 and 2.3{+/-}0.5 ng/mL, respectively), and decreasing to basal levels in juvenile frogs. In contrast, 3,5-diiodothyronine (T2) increased significantly at Gosner stage 40 and was maintained elevated until stage 44. While thra transcript levels remained constant and then decreased at the end of metamorphic climax, thrb and thibz were induced to maximal levels at Gosner stage 41, followed by a decrease to basal levels in the froglet. This exemplifies the exquisite timing of events during metamorphosis as classic early response genes are transcribed in anticipation of peak TH concentrations. The distinct T2 concentration profile suggests a biological role of this biomolecule in anuran postembryonic development and an additional aspect that may be a target of anthropogenic chemicals that can disrupt anuran metamorphosis and TH signalling. Hence, as a second aim of the study, we set out to find additional bioindicators of metamorphosis, which can aid future investigations of developmental disruption. Using a sensitive nanoLC-Orbitrap system an untargeted analysis workflow was applied. Among 6,062 endogenous metabolites, 421 showed metamorphosis-dependent concentration dynamics. These potential bioindicators included several carnitines, prostaglandins and some steroid hormones.

developmental biology↗

bioRxiv2022

Environmental gradients reveal stress hubs predating plant terrestrialization

Plant terrestrialization brought forth the land plants (embryophytes). Embryophytes account for most of the biomass on land and evolved from streptophyte algae in a singular event. Recent advances have unraveled the first full genomes of the closest algal relatives of land plants; among the first such species was Mesotaenium endlicherianum. Here, we used fine-combed RNAseq in tandem with photophysiological assessment on Mesotaenium exposed to a continuous range of temperature and light cues. Our data establish a grid of 42 different conditions, resulting in 128 transcriptomes and ~1.5 Tbp (~9.9 billion reads) of data to study combinatory effects of stress response using clustering along gradients. We describe major hubs in genetic networks underpinning stress response and acclimation in the molecular physiology of Mesotaenium. Our data suggest that lipid droplet formation, plastid and cell wall-derived signals denominate molecular programs since more than 600 million years of streptophyte evolution--before plants made their first steps on land.

evolutionary biology↗