Featured
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Article
| Open AccessSynthetic intrinsically disordered protein fusion tags that enhance protein solubility
Insoluble protein expression continues to be a bottleneck for biotechnology. Here, Chilkoti and colleagues report a method for generating and identifying hypersoluble intrinsically disordered protein fusion tags to improve soluble protein expression and rescue protein function.
- Nicholas C. Tang
- , Jonathan C. Su
- & Ashutosh Chilkoti
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Article
| Open AccessSkin graft with dermis and appendages generated in vivo by cell competition
Skin substitutes generated by tissue engineering have limited properties. Here, authors established niche encroachment method. Cell competition enabled skin organogenesis from allogeneic and xenogeneic stem cells on p63 knockout embryos, resulting in a complete skin graft on dermis with hair.
- Hisato Nagano
- , Naoaki Mizuno
- & Hiromitsu Nakauchi
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Perspective
| Open AccessEngineering is evolution: a perspective on design processes to engineer biology
Evolutionary and rational design approaches are commonly used to engineer biological systems but are typically seen at odds with each other. In this perspective the authors argue for the concept of an evolutionary design spectrum to help unify and compare these design methodologies to support more effective biological engineering.
- Simeon D. Castle
- , Michiel Stock
- & Thomas E. Gorochowski
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Article
| Open AccessDiscovering a mitochondrion-localized BAHD acyltransferase involved in calystegine biosynthesis and engineering the production of 3β-tigloyloxytropane
A mitochondrion-localised BAHD acyltransferase (3β-tigloyloxytropane synthase, TS) from Atropa belladonna is responsible for the formation of 3β-tigloyloxytropane, the key intermediate in calystegine biosynthesis.
- Junlan Zeng
- , Xiaoqiang Liu
- & Zhihua Liao
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Article
| Open AccessA vascularized breast cancer spheroid platform for the ranked evaluation of tumor microenvironment-targeted drugs by light sheet fluorescence microscopy
Assessing tumour microenvironment-targeted drug candidates remains challenging. Here, the authors develop a comprehensive screening platform that allows for monitoring, quantifying, and ranking drug-induced effects in self-organizing, vascularized tumour spheroids.
- David Ascheid
- , Magdalena Baumann
- & Erik Henke
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Article
| Open AccessThe hinge-engineered IgG1-IgG3 hybrid subclass IgGh47 potently enhances Fc-mediated function of anti-streptococcal and SARS-CoV-2 antibodies
Here, the authors elongated the hinge structure of IgG1 monoclonal antibodies. The modified IgG1-IgG3 hybrid subclass showed enhanced Fc-mediated function compared to IgG1 in two distinct biological systems, Streptococcus pyogenes and SARS-CoV-2.
- Arman Izadi
- , Yasaman Karami
- & Pontus Nordenfelt
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Article
| Open AccessscLENS: data-driven signal detection for unbiased scRNA-seq data analysis
Single-cell RNA sequencing data analysis is limited by noise and high dimensionality. Here, authors present scLENS, a tool that automates accurate signal detection without manual input, particularly in complex datasets.
- Hyun Kim
- , Won Chang
- & Jae Kyoung Kim
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Article
| Open AccessEfficient gene knockout and genetic interaction screening using the in4mer CRISPR/Cas12a multiplex knockout platform
Paralog synthetic lethals have been assessed with multiple CRISPR-based methods, but systematic comparison among these platforms is unavailable. Here, the authors systematically compare combinatorial perturbation platforms and establish the in4mer CRISPR/Cas12a multiplex knockout platform.
- Nazanin Esmaeili Anvar
- , Chenchu Lin
- & Traver Hart
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Article
| Open AccessStimulus-responsive assembly of nonviral nucleocapsids
A stimulus-responsive approach for recapitulating nonviral nucleocapsid assembly on demand under controlled conditions provides a robust platform for applications in synthetic biology and mRNA nanomedicine.
- Mao Hori
- , Angela Steinauer
- & Donald Hilvert
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Article
| Open AccessA mechanical-assisted post-bioprinting strategy for challenging bone defects repair
Bioprinting has revitalized tissue regeneration efforts, yet challenges persist due to cell damage during fabrication and mechanical instability of printed scaffolds. Here, the authors develop a mechanical-assisted post-bioprinting strategy for loading cells into hollow scaffolds that effectively repair challenging bone defects.
- Jirong Yang
- , Zhigang Chen
- & Changshun Ruan
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Article
| Open AccessUnravelling and reconstructing the biosynthetic pathway of bergenin
Bergenin is a rare C-glycoside of 4-O-methyl gallic acid with multiple pharmacological properties. Here, the authors report the elucidation of the biosynthetic pathway of bergenin in Ardisia japonica and its bioproduction by engineered E. coli.
- Ruiqi Yan
- , Binghan Xie
- & Lin Yang
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Article
| Open AccessControl of polymers’ amorphous-crystalline transition enables miniaturization and multifunctional integration for hydrogel bioelectronics
Soft elastic materials could be useful in the fabrication of brain-machine interfaces, but achieving the desirable material properties can be challenging. Here, the authors report control of the amorphous-crystalline transition of polymers to alter hydrogel properties and monitor mouse behaviour.
- Sizhe Huang
- , Xinyue Liu
- & Siyuan Rao
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Perspective
| Open AccessAutomated in vivo enzyme engineering accelerates biocatalyst optimization
Achieving cost-competitive bio-based processes requires development of stable and selective biocatalysts. In this Perspective, the authors propose an integrated solution combining growth-coupled selection with machine learning and automated workflows to accelerate development pipelines.
- Enrico Orsi
- , Lennart Schada von Borzyskowski
- & Steffen N. Lindner
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Article
| Open AccessCoCas9 is a compact nuclease from the human microbiome for efficient and precise genome editing
Cas9 nucleases hold clinical significance for genome editing therapies. Here the authors characterize CoCas9, a compact, efficient and precise Cas9 from the human microbiome, and show that delivery via AAV vectors enables efficient editing in the mouse retina, expanding the genome editing toolbox.
- Eleonora Pedrazzoli
- , Michele Demozzi
- & Anna Cereseto
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Article
| Open AccessStructural and biochemical analysis of family 92 carbohydrate-binding modules uncovers multivalent binding to β-glucans
Carbohydrate binding modules (CBMs) are non-catalytic domains found within multi-modular carbohydrate-active enzymes like glycoside hydrolases. Here, the authors show the crystal structures of two CBM family 92 members, which use three different surface binding sites to bind to β-glucans.
- Meng-Shu Hao
- , Scott Mazurkewich
- & Lauren S. McKee
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Article
| Open AccessIntegrating taxonomic signals from MAGs and contigs improves read annotation and taxonomic profiling of metagenomes
Metagenomic taxonomic profiling usually relies either on reads or assembled contigs/MAGs. Here, authors present RAT, a tool that integrates taxonomic signals from reads, contigs, and MAGs into one profile with high precision and sensitivity. RAT provides a comprehensive view of the microbiome.
- Ernestina Hauptfeld
- , Nikolaos Pappas
- & F. A. Bastiaan von Meijenfeldt
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Article
| Open AccessA patient-specific lung cancer assembloid model with heterogeneous tumor microenvironments
Realistic tumour models are critical for the development of clinically relevant treatments. Here, the authors develop a lung cancer assembloid model which recapitulates key components of the primary tumour, and can be used to predict clinical outcome.
- Yanmei Zhang
- , Qifan Hu
- & Zhuo Xiong
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Article
| Open AccessLocal environment in biomolecular condensates modulates enzymatic activity across length scales
Here, the authors show that biomolecular condensates can enhance enzymatic rates by creating distinct solvent environments compared to the surrounding solution, and this emergent property can manifest within assemblies as small as nanometers.
- Marcos Gil-Garcia
- , Ana I. Benítez-Mateos
- & Paolo Arosio
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Article
| Open AccessEngineering a synthetic gene circuit for high-performance inducible expression in mammalian systems
Inducible gene expression systems can be used to control the expression of a gene of interest by means of small molecules. Here the authors present CASwitch, a synthetic gene circuit platform enhancing inducible gene expression systems by reducing leakiness and boosting fold induction, for real world applications like gene therapy vector production and biosensors.
- Giuliano De Carluccio
- , Virginia Fusco
- & Diego di Bernardo
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Article
| Open AccessThe physiological interactome of TCR-like antibody therapeutics in human tissues
The use of bispecific antibodies to target tumour-specific epitopes presented by MHC molecules in tumour tissue is a promising avenue for cancer immunotherapy. Here the authors use a mass-spectrometry guided analysis to identify off-target MHC-peptide complexes that bind to TCR-like antibodies next to the target peptide, enabling a novel approach to monitoring of antibody specificity during clinical maturation and development.
- Estelle Marrer-Berger
- , Annalisa Nicastri
- & Nicola Ternette
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Article
| Open AccessX-ray-activated polymerization expanding the frontiers of deep-tissue hydrogel formation
Photo-crosslinking polymerization facilitates precise control of hydrogel formation for various applications including tissue engineering, but most existing photo-crosslinking methods fail to achieve deep-tissue penetration, especially within bone structures. Here the authors report a strategy of low-dose X-ray-activated polymerization that enables deep-tissue hydrogel formation.
- Hailei Zhang
- , Boyan Tang
- & Gang Han
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Article
| Open AccessA modular and synthetic biosynthesis platform for de novo production of diverse halogenated tryptophan-derived molecules
De novo fermentation and synthetic pathway construction for halogen-containing molecules remain relatively underexplored. Here, the authors report a mix-and-match co-culture platform to de novo generate a large array of halogenated tryptophan derivatives in E. coli from glucose.
- Kevin B. Reed
- , Sierra M. Brooks
- & Hal S. Alper
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Article
| Open AccessMultiscale architecture design of 3D printed biodegradable Zn-based porous scaffolds for immunomodulatory osteogenesis
Rapid degradation inducing overdose toxicity remains challenging in porous biodegradable bone scaffolds. Here the authors present multiscale architecture design on ZnLi scaffolds with 90% porosity orchestrates immune responses and subsequent bone regeneration.
- Shuang Li
- , Hongtao Yang
- & Yufeng Zheng
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Article
| Open AccessHydrophobic mismatch drives self-organization of designer proteins into synthetic membranes
The organization of membrane proteins is critical to cellular function. Here the authors explore how computational protein design, MD simulation, and cell-free systems can be combined to elucidate how membrane-protein hydrophobic mismatch affects protein folding and organization in synthetic lipid membranes.
- Justin A. Peruzzi
- , Jan Steinkühler
- & Neha P. Kamat
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Article
| Open AccessKSNP: a fast de Bruijn graph-based haplotyping tool approaching data-in time cost
Haplotyping is the process of distinguishing alleles inherited together on a chromosome, a crucial step in assembling and interpreting genome sequences. Here, the authors present a computationally efficient haplotype assembly tool for long read sequencing data.
- Qian Zhou
- , Fahu Ji
- & Jue Ruan
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Article
| Open AccessComplex activity and short-term plasticity of human cerebral organoids reciprocally connected with axons
Connecting cerebral organoids with an axon bundle models inter-regional projections and enhances neural activity. Optogenetic stimulation induces short-term plasticity, offering insights into macroscopic circuit development and functionality.
- Tatsuya Osaki
- , Tomoya Duenki
- & Yoshiho Ikeuchi
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Article
| Open AccessscButterfly: a versatile single-cell cross-modality translation method via dual-aligned variational autoencoders
Technical limitations of simultaneously multi-omics profiling lead to highly noisy multi-modal data and substantial costs. Here, authors proposed a versatile framework and data augmentation schemes, capable of single-cell cross-modality translation and multiple extensive applications.
- Yichuan Cao
- , Xiamiao Zhao
- & Shengquan Chen
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Article
| Open AccessContext-aware deep learning enables high-efficacy localization of high concentration microbubbles for super-resolution ultrasound localization microscopy
Ultrasound localisation microscopy enables deep tissue microvascular imaging. Here, authors introduce LOCA-ULM, a deep learning pipeline enhancing localisation accuracy in high microbubble concentrations. LOCA-ULM reveals dense cerebrovascular networks and enhances the sensitivity of functional ULM.
- YiRang Shin
- , Matthew R. Lowerison
- & Pengfei Song
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Article
| Open AccessThe CRISPR-Cas13a Gemini System for noncontiguous target RNA activation
CRISPR-Cas13a based methods currently use contiguous target RNA activation, which only enables single-target detection or editing. Here the authors propose a noncontiguous target RNA activation approach which can provide rapid, simultaneous and sensitive detection of two RNAs in a single readout, as well as parallel dual transgene knockdown.
- Hongrui Zhao
- , Yan Sheng
- & Jiaming Hu
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Article
| Open AccessVISTA checkpoint inhibition by pH-selective antibody SNS-101 with optimized safety and pharmacokinetic profiles enhances PD-1 response
VISTA is a pH-dependent inhibitory checkpoint for T-cells that is abundant on myeloid lineage cells and antagonists of VISTA may successfully reinvigorate anti-tumour immunity. Here, the authors show that the antibody SNS-101, which is currently being investigated in humans in a clinical trial, is characterized by pH-sensitivity that endows it with favorable pharmacokinetic and safety profiles, and enhanced therapeutic effect when combined with PD-1 checkpoint inhibitors.
- Thomas Thisted
- , F. Donelson Smith
- & Edward H. van der Horst
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Article
| Open AccessEarly detection of emerging viral variants through analysis of community structure of coordinated substitution networks
Rise of new viral strains is a major public health challenge, demanding advanced detection and forecasting methods. This study shows how examining communities within networks of viral mutations enables early detection of emerging strains.
- Fatemeh Mohebbi
- , Alex Zelikovsky
- & Pavel Skums
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Article
| Open AccessPianno: a probabilistic framework automating semantic annotation for spatial transcriptomics
Recognising spatial spots’ biological identity in spatial transcriptomics remains a challenge. Here, authors introduce Pianno, a tool that helps annotate the biological structures or cell-type constructions across diverse tissues, offering new perspectives on understanding spatial transcriptomics.
- Yuqiu Zhou
- , Wei He
- & Ying Zhu
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Article
| Open AccessBiomimetic NIR-II fluorescent proteins created from chemogenic protein-seeking dyes for multicolor deep-tissue bioimaging
Near-infrared-I/II fluorescent proteins (NIR-I/II FPs) are crucial for in vivo imaging, but their availability is still scarce. Here, the authors make use of protein-seeking NIR-II dyes as chromophores, which covalently bind to tag proteins and thus creating biomimetic NIR-II FPs.
- Jiajun Xu
- , Ningning Zhu
- & Shoujun Zhu
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Article
| Open AccessPLMSearch: Protein language model powers accurate and fast sequence search for remote homology
Homologous protein search is one of the most commonly used methods for protein analysis. Here, authors propose PLMSearch, a search method that takes only sequences as input and can search millions of protein pairs in seconds while maintaining sensitivity comparable to SOTA structure search methods.
- Wei Liu
- , Ziye Wang
- & Shanfeng Zhu
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Article
| Open AccessCell surface patching via CXCR4-targeted nanothreads for cancer metastasis inhibition
CXCR4-targeted therapies have been proposed for the treatment of cancer metastasis. Here the authors propose a CXCR4-targeted strategy based on interactable polymer nanothreads, showing inhibition of metastasis in preclinical cancer models.
- Minglu Zhou
- , Chendong Liu
- & Lian Li
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Article
| Open AccessMicrointerfaces in biopolymer-based bicontinuous hydrogels guide rapid 3D cell migration
Extracellular microinterfaces provide cells with migration tracks in vivo. Here, the authors introduce these microtracks into bicontinuous hydrogels to elicit rapid cell migration in 3-dimensional contexts.
- Karen L. Xu
- , Nikolas Di Caprio
- & Jason A. Burdick
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Article
| Open AccessGene-expression memory-based prediction of cell lineages from scRNA-seq datasets
Combining experimental lineage tracing with single cell transcriptomics is technically demanding. Here, authors present GEMLI, a computational tool to annotate cell lineages in single cell RNA sequencing data solely based on gene expression.
- A. S. Eisele
- , M. Tarbier
- & D. M. Suter
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Article
| Open AccessDELVE: feature selection for preserving biological trajectories in single-cell data
Characteristic genes or proteins driving continuous biological processes are difficult to uncover from noisy single-cell data. Here, authors present DELVE, an unsupervised feature selection method to identify core molecular features driving cell fate decisions.
- Jolene S. Ranek
- , Wayne Stallaert
- & Jeremy E. Purvis
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Article
| Open AccessBioorthogonal photocatalytic proximity labeling in primary living samples
Studying subcellular proteomes in primary living cells is crucial for understanding health and disease. Here, the authors introduce CAT-S, a non-genetic method based on photocatalysis, enabling in situ deciphering of mitochondrial proteomes in primary cells from mouse tissues and human blood.
- Ziqi Liu
- , Fuhu Guo
- & Xinyuan Fan
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Article
| Open AccessRegulatory T cells expressing CD19-targeted chimeric antigen receptor restore homeostasis in Systemic Lupus Erythematosus
Systemic Lupus Erythematosus (SLE) is a chronic and progressive autoimmune disease characterized by abnormally activated B cells causing organ damage. Here authors introduce an adoptive cell therapy involving regulatory T cells overexpressing FoxP3 and harboring an anti-CD19 CAR to inhibit pathological B cells and thus tissue-harming autoimmunity in a humanized mouse model.
- M. Doglio
- , A. Ugolini
- & C. Bonini
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Article
| Open AccessSilk fibroin hydrogel adhesive enables sealed-tight reconstruction of meniscus tears
Suture repair is the current clinical treatment for meniscus tears, but inaccessible tears in company with re-tears susceptibility remain unresolved. Here the authors address these issues by developing a meniscus adhesive-based strategy for the seamless and dense reconstruction of torn meniscus.
- Xihao Pan
- , Rui Li
- & Hongwei Ouyang
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Article
| Open AccessA dual diffusion model enables 3D molecule generation and lead optimization based on target pockets
Structure-based generative chemistry is crucial in computer-aided drug discovery. Here, authors propose PMDM, a conditional generative model for 3D molecule generation tailored to specific targets. Extensive experiments demonstrate that PMDM can effectively generate rational bioactive molecules
- Lei Huang
- , Tingyang Xu
- & Hengtong Zhang
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Article
| Open AccessPredicting and improving complex beer flavor through machine learning
Perception and appreciation of food flavour depends on many factors, posing a challenge for effective prediction. Here, the authors combine extensive chemical and sensory analyses of 250 commercial Belgian beers to train machine learning models that enable flavour and consumer appreciation prediction.
- Michiel Schreurs
- , Supinya Piampongsant
- & Kevin J. Verstrepen
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Article
| Open AccessSynthetically-primed adaptation of Pseudomonas putida to a non-native substrate D-xylose
Pseudomonas putida is becoming a host of choice for the valorization of lignocellulosic substrates. Here, the authors provide insight into the adaptation of this bacterium to the non-native substrate D-xylose, enabled by metabolic engineering and adaptive laboratory evolution.
- Pavel Dvořák
- , Barbora Burýšková
- & Martin Benešík
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Article
| Open AccessFunctional screening in human HSPCs identifies optimized protein-based enhancers of Homology Directed Repair
Here the authors describe a functional screening platform in human stem cells to identify and optimize protein-based gene editing additives that increase homologous directed recombination and have potential to improve gene therapy workflows.
- Juan A. Perez-Bermejo
- , Oghene Efagene
- & Kristen L. Seim
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Article
| Open AccessDevelopmental progression of DNA double-strand break repair deciphered by a single-allele resolution mutation classifier
DNA double-strand breaks (DSBs) are repaired by a hierarchically regulated network of pathways. Here, authors develop ICP for deciphering somatic DSB repair patterns in multicellular organisms and discover developmental regulation in flies and mosquitoes, enabling tracking of mutant alleles and interhomolog copying of gene cassettes.
- Zhiqian Li
- , Lang You
- & Ethan Bier
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Article
| Open AccessVersatile human cardiac tissues engineered with perfusable heart extracellular microenvironment for biomedical applications
The application of engineered cardiac tissues is limited due to their immaturity and lack of functionality. Here, the authors develop an integrated culture platform featuring heart extracellular matrix cultured in a microfluidic chip to facilitate cardiac tissue development for versatile biomedical applications.
- Sungjin Min
- , Suran Kim
- & Seung-Woo Cho
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Article
| Open AccessA let-7 microRNA-RALB axis links the immune properties of iPSC-derived megakaryocytes with platelet producibility
The authors pioneered the iPSC-derived platelet transfusion in human. Here they employ miRNA switches, identifying RALB as a determinant of immune megakaryocytes and a marker for quality control, advancing standardization of iPSC-platelet production.
- Si Jing Chen
- , Kazuya Hashimoto
- & Koji Eto
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Review Article
| Open AccessArtificial cells for in vivo biomedical applications through red blood cell biomimicry
Despite the enormous progress in the field of giant lipid vesicles, their use for in vivo biomedical applications is limited. Here, the authors discuss red blood cells as inspiration for enhancing those vesicles, investigating the required cellular features and the corresponding technical hurdles.
- Jorik Waeterschoot
- , Willemien Gosselé
- & Xavier Casadevall i Solvas
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