Biology subjects

Natu, V.

Publications and source records attributed to Natu, V..

7 recordsLinked to original sources

bioRxiv2026

Multiphasic myelination and dendritic growth modulate qMRI signals in human visual cortex.

How does myelin develop in human visual cortex? By combining immunohistochemistry with in vivo and postmortem magnetic resonance imaging of longitudinal relaxation rate (R1), which increases with myelin content, we find that myelin and R1 increase across development but follow distinct trajectories. Immunohistochemistry reveals two phases of myelination: an infant phase of limited oligodendrogenesis, with myelin restricted to deep cortical layers, followed by widespread myelination across all layers during childhood. Cortical R1 also increases across development and correlates with myelin by childhood. However, in infancy, R1 increases outpace myelin growth and instead tracks dendritic arborization, indicating that the microstructural drivers of R1 change across development. We hypothesize that deep layer myelination in infancy contributes to early visual function whereas later myelination of superficial layers enables prolonged cortical plasticity and learning of complex visual behaviors.

neuroscience↗

bioRxiv2026

Platelets Outperform Leukocytes in Transcriptomic Liquid Biopsy Profiling of Myeloproliferative Neoplasms

Myeloproliferative neoplasms (MPNs) are characterized by progressive myelofibrosis that drives morbidity and mortality. Liquid biopsy approaches to noninvasively monitor fibrotic progression remain limited. We performed comparative transcriptomic profiling of CD45-depleted platelet-enriched and CD45+ leukocyte-enriched fractions from matched peripheral blood samples of 76 individuals (27 primary myelofibrosis, 17 polycythemia vera, 14 essential thrombocythemia, 18 healthy controls). Platelet RNA sequencing was performed in 2018-2020 on Illumina HiSeq 4000, while WBC RNA sequencing was conducted in 2023 on Illumina NovaSeq 6000 from cryopreserved CD45+ enriched fractions of specimens obtained at the identical time and from the same blood sample as the platelet RNA. Despite comparable library preparation protocols and higher sequencing depth in WBC samples, platelet transcriptomes exhibited 5.1-fold more differential expression in myelofibrosis (3,453 versus 681 genes, adjusted p<0.05, |log2FC|>1). Platelet signatures were enriched for proteostasis pathways including endoplasmic reticulum stress and unfolded protein response, reflecting megakaryocyte dysfunction in the fibrotic bone marrow niche. WBC signatures predominantly featured immune activation and proliferative pathways, indicating systemic inflammatory responses. Multinomial LASSO classification demonstrated superior performance of platelet-based models for myelofibrosis diagnosis (AUROC 0.85) compared to WBC-based (AUROC 0.77) or clinical models (AUROC 0.59). Combined platelet+WBC models did not improve performance (AUROC 0.80), indicating complementary but non-additive information. These findings establish platelet transcriptomic profiling as a superior noninvasive biomarker platform for monitoring myelofibrosis in MPNs, capturing megakaryocyte-driven fibrogenesis with greater sensitivity than peripheral leukocyte-based approaches. HighlightsUsing matched WBC and platelet RNA-seq from MPN patients, we identify myelofibrosis-associated transcriptomic signatures specifically enriched in platelets. Multinomial LASSO modeling highlights platelet-derived gene expression as a dominant and predictive biomarker of myelofibrosis, outperforming clinical parameters and WBC signatures. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=75 SRC="FIGDIR/small/714941v1_ufig1.gif" ALT="Figure 1"> View larger version (21K): org.highwire.dtl.DTLVardef@10a388borg.highwire.dtl.DTLVardef@66079org.highwire.dtl.DTLVardef@a7c29eorg.highwire.dtl.DTLVardef@1da1a96_HPS_FORMAT_FIGEXP M_FIG C_FIG

pathology↗

bioRxiv2021

Catch me if you can: Least myelinated white matter develops fastest during early infancy

Development of myelin, a fatty sheath that insulates nerve fibers, is critical for brain function. Myelination during infancy has been studied with histology, but postmortem data cannot evaluate the longitudinal trajectory of white matter development. Here, we obtained longitudinal diffusion MRI and quantitative MRI measures of R1 in 0, 3 and 6 months-old human infants, and (ii) developed an automated method to identify white matter bundles and quantify their properties in each infants brain. We find that R1 increases from newborns to 6-months-olds in all bundles. R1 development is nonuniform: there is faster development in white matter that is less mature in newborns, and along inferior-to-superior as well as anterior-to-posterior spatial gradients. As R1 is linearly related to myelin fraction in white matter bundles, these findings open new avenues to elucidate typical and atypical white matter myelination in early infancy, which has important implications for early identification of neurodevelopmental disorders.

neuroscience↗

bioRxiv2021

Progressive and predictive markers of disease evolution: platelet transcriptome in chronic myeloproliferative neoplasms

Predicting disease progression remains a particularly challenging endeavor in chronic degenerative disorders and cancer, thus limiting early detection, risk stratification, and preventive interventions. Here, profiling the spectrum of chronic myeloproliferative neoplasms (MPNs) as a model, we identify the blood platelet transcriptome as a proxy for highly sensitive progression biomarkers that also enables prediction of advanced disease via machine learning algorithms. Using RNA sequencing (RNA-seq), we derive disease-relevant gene expression in purified platelets from 120 peripheral blood samples constituting two time-separated cohorts of patients diagnosed with one of three MPN subtypes at sample acquisition - essential thrombocythemia, ET (n=24), polycythemia vera, PV (n=33), and primary or post ET/PV secondary myelofibrosis, MF (n=42), and healthy donors (n=21). The MPN platelet transcriptome reveals an incremental molecular reprogramming that is independent of patient driver mutation status or therapy and discriminates each clinical phenotype. Leveraging this dataset that shows a characteristic progressive expression gradient across MPN, we develop a machine learning model (Lasso-penalized regression) and predict advanced subtype MF at high accuracy and under two conditions of external validation: i) temporal: our two Stanford cohorts, AUC-ROC of 0.96; and ii) geographical: independently published data of an additional n=25 MF and n=46 healthy donors, AUC-ROC of 0.97). Lasso-derived signatures offer a robust core set of < 5 MPN transcriptome markers that are progressive in expression. Mechanistic insights from our data highlight impaired protein homeostasis as a prominent driver of MPN evolution, with persistent integrated stress response. We also identify JAK inhibitor-specific signatures and other interferon, proliferation, and proteostasis-associated markers as putative targets for MPN-directed therapy. Our platelet transcriptome snapshot of chronic MPNs demonstrates a proof of principle for disease risk stratification and progression beyond genetic data alone, with potential utility in other progressive disorders. HighlightsLeveraging two independent and mutually validating MPN patient cohorts, we identify progressive transcriptomic markers that also enable externally validated prediction in MPNs. Our platelet RNA-Seq data identifies impaired protein homeostasis as prominent in MPN progression and offers putative targets of therapy. VISUAL ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=135 HEIGHT=200 SRC="FIGDIR/small/435190v3_ufig1.gif" ALT="Figure 1"> View larger version (42K): org.highwire.dtl.DTLVardef@72dc16org.highwire.dtl.DTLVardef@cf5096org.highwire.dtl.DTLVardef@b3d460org.highwire.dtl.DTLVardef@3c0ddc_HPS_FORMAT_FIGEXP M_FIG C_FIG

genomics↗

bioRxiv2020

Cortical recycling in high-level visual cortex during childhood development

Human ventral temporal cortex (VTC) contains category-selective regions that respond preferentially to ecologically-relevant categories such as faces, bodies, places, and words, which are causally involved in the perception of these categories. How do these regions develop during childhood? We used functional MRI to measure longitudinal development of category-selectivity in school-age children over 1 to 5 years. We discovered that from young childhood to the teens, face- and word-selective regions in VTC expand and become more category-selective, but limb-selective regions shrink and lose their preference for limbs. Critically, as a child develops, increases in face- and word-selectivity are directly linked to decreases in limb-selectivity, revealing that during childhood limb-selectivity in VTC is repurposed into word- and face-selectivity. These data provide evidence for cortical recycling during childhood development. This has important implications for understanding typical as well as atypical brain development and necessitates a rethinking of how cortical function develops during childhood.

neuroscience↗

bioRxiv2018

Learning to read increases the informativeness of distributed ventral temporal responses

Becoming a proficient reader requires substantial learning over many years. However, it is unknown how learning to read affects development of distributed visual representations across human ventral temporal cortex (VTC). Using fMRI and a data-driven, computational approach, we quantified the development of distributed VTC responses to characters (pseudowords and numbers) vs. other domains in children, preteens, and adults. Results reveal anatomical- and hemisphere-specific development. With development, distributed responses to words and characters became more distinctive and informative in lateral but not medial VTC, and in the left but not right hemisphere. While development of voxels with both positive (that is, word-selective) and negative preference to words affected distributed information, only development of word-selective voxels predicted reading ability. These data show that developmental increases in informativeness of distributed left lateral VTC responses enable proficient reading and have important implications for both developmental theories and for elucidating neural mechanisms of reading disabilities.

neuroscience↗

bioRxiv2017

Development differentially sculpts receptive fields across human visual cortex

Receptive fields (RFs) processing information in restricted parts of the visual field are a key property of neurons in the visual system. However, how RFs develop in humans is unknown. Using fMRI and population receptive field (pRF) modeling in children and adults, we determined where and how pRFs develop across the ventral visual stream. We find that pRF properties in visual field maps, V1 through VO1, are adult-like by age 5. However, pRF properties in face- and word-selective regions develop into adulthood, increasing the foveal representation and the visual field coverage for faces in the right hemisphere and words in the left hemisphere. Eye-tracking indicates that pRF changes are related to changing fixation patterns on words and faces across development. These findings suggest a link between viewing behavior of faces and words and the differential development of pRFs across visual cortex, potentially due to competition on foveal coverage.

neuroscience↗