Biology subjects

D'Amato, C.

Publications and source records attributed to D'Amato, C..

5 recordsLinked to original sources

bioRxiv2025

Microbiome-behavior coupling shapes infant adaptation to early maternal unpredictability

We asked whether infant microbiome composition, together with infants behavioral responses to early maternal unpredictability, can offer novel mechanistic insights into behavioral phenotypic variation in human development. Maternal unpredictability was computed as the entropy rate of transitions among maternal sensory signals during naturalistic mother-infant interaction (n=256 dyads; 2-6 months). Infant visual orienting behavior (VOB) was indexed by infants simultaneous gaze shifts to and from the mother. Higher maternal unpredictability predicted more frequent VOB shifts, indicating a mature-for-age profile, and longitudinally forecast poorer inhibitory control at 19-28 months. A subgroup of infants with high maternal unpredictability and high VOB had inhibitory control outcomes closer to those of infants who experienced low maternal unpredictability, suggesting VOB strategy might buffer against the effects of high maternal unpredictability. In participants with metagenomic data (n=93), VOB was associated with taxonomic and functional gut microbial profiles along a Bifidobacterium breve to Bifidobacterium longum axis. Neuroactive gene-set enrichment analysis linked VOB to increase in tryptophan synthesis and glutamate synthesis genes. In contrast, maternal unpredictability showed depletions of GABA and tryptophan synthesis in the unique-effects model and, when VOB and the maternal unpredictability by VOB term were included, enrichment of acetate synthesis and quinolinic acid degradation. Notably, the maternal unpredictability by VOB interactions for tryptophan and glutamate were negative, indicating that the VOB-pathway coupling attenuates as unpredictability increases. Together, these findings support a framework in which maternal unpredictability is the environmental challenge, infant VOB expresses the behavioral strategy, and microbial metabolism modulates whether that strategy is biochemically feasible. TeaserInfant gut microbiome is linked to infant behavioral responses to maternal unpredictability, which in turn impacts how they learn to control their actions.

neuroscience↗

bioRxiv2024

Intrinsic molecular identifiers enable robust molecular counting in single-cell sequencing

Particle-templated instant partition sequencing (PIPseq), is an emerging approach for massively scalable single-cell gene expression studies that does not require complex instrumentation or expensive consumables. We present PIPseqTM V, a novel implementation of the PIPseq workflow with significant improvements in assay performance and sensitivity compared to prior methods. Among the innovations driving the improved performance in PIPseq V is a new approach for transcript counting using Intrinsic Molecular Identifiers (IMIs) from the captured transcript sequence, eliminating the need for traditional Unique Molecular Identifiers (UMIs). IMIs are the starting positions for molecules generated by random fragmentation after limited cycle PCR, which can be used to uniquely identify individual transcript copies of genes expressed within individual cells. To correct for experimental variation in IMI generation, we have developed a dynamic correction strategy that can adapt to different sample cell input, transcript expression, and sequencing depth without the need for external benchmarking or controls. Our results demonstrate that PIPseq V with IMI-based analysis provides biological information comparable to established UMI-based approaches while avoiding UMI-associated biases. Dynamic correction offers a robust and data-driven analysis strategy for scRNAseq.

genomics↗

bioRxiv2023

Multiomic Single Cell Sequencing Identifies Stemlike Nature of Mixed Phenotype Acute Leukemia and Provides Novel Risk Stratification

Mixed phenotype acute leukemia (MPAL) is a leukemia whose biologic drivers are poorly understood, therapeutic strategy remains unclear, and prognosis is poor. We performed multiomic single cell (SC) profiling of 14 newly diagnosed adult MPAL patients to characterize the immunophenotypic, genetic, and transcriptional landscapes of MPAL. We show that neither genetic profile nor transcriptome reliably correlate with specific MPAL immunophenotypes. However, progressive acquisition of mutations is associated with increased expression of immunophenotypic markers of immaturity. Using SC transcriptional profiling, we find that MPAL blasts express a stem cell-like transcriptional profile distinct from other acute leukemias and indicative of high differentiation potential. Further, patients with the highest differentiation potential demonstrated inferior survival in our dataset. A gene set score, MPAL95, derived from genes highly enriched in this cohort, is applicable to bulk RNA sequencing data and was predictive of survival in an independent patient cohort, suggesting utility for clinical risk stratification.

cancer biology↗

bioRxiv2022

Microfluidics-free single-cell genomics with templated emulsification

Single-cell RNA sequencing is now a standard method used to reveal the molecular details of cellular heterogeneity, but current approaches have limitations on speed, scale, and ease of use that stem from the complex microfluidic devices or fluid handling steps required for sample processing. We, therefore, developed a method that does not require specialized microfluidic devices, expertise, or hardware. Our approach is based on particle-templated emulsification, which allows single-cell encapsulation and barcoding of cDNA in uniform droplet emulsions with only a vortexer. PIP-seq accommodates a wide range of emulsification formats, including microwell plates and large-volume conical tubes, enabling thousands of samples or millions of cells to be processed in minutes. We demonstrate that PIP-seq produces high-purity transcriptomes in mouse-human mixing studies, is compatible with multi-omics measurements, and can accurately characterize cell types in human breast tissue when compared to a commercial microfluidic platform. Single-cell transcriptional profiling of mixed phenotype acute leukemia using PIP-seq revealed the emergence of heterogeneity within chemotherapy-resistant cell subsets that were hidden by standard immunophenotyping. PIP-seq is a simple, flexible, and scalable next-generation workflow that extends single-cell sequencing to new applications, including screening, diagnostics, and disease monitoring.

genomics↗

bioRxiv2021

Transcription factor induction of vascular blood stem cell niches in vivo

The hematopoietic niche is a supportive microenvironment comprised of distinct cell types, including specialized vascular endothelial cells that directly interact with hematopoietic stem and progenitor cells (HSPCs). The molecular factors that specify niche endothelial cells and orchestrate HSPC homeostasis remain largely unknown. Using multi-dimensional gene expression and chromatin accessibility analyses, we define a conserved gene expression signature and cis-regulatory landscape unique to sinusoidal endothelial cells in the HSPC niche. Using enhancer mutagenesis and transcription factor overexpression, we elucidate a transcriptional code involving members of the Ets, Sox and Nuclear Hormone Receptor families that is sufficient to induce ectopic niche endothelial cells that associate with mesenchymal stromal cells and support the recruitment, maintenance and division of HSPCs in vivo. These studies set forth an approach for generating synthetic HSPC niches, in vitro or in vivo, and for effective therapies to modulate the endogenous niche.

developmental biology↗