BASELINE: A CRISPR Base Editing Platform for Mammalian-Scale Single-Cell Lineage Tracing DOI Open Access

Eitan Winter,

Francesco E. Emiliani,

Arthur C. Cook

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown

Опубликована: Март 20, 2025

A cell's fate is shaped by its inherited state, or lineage, and the ever-shifting context of environment. CRISPR-based recording technologies are a promising solution to map lineage developing system, yet challenges remain regarding single-cell recovery, engineering complexity, scale. Here, we introduce BASELINE, which uses base editing generate high-resolution trees in conjunction with profiling. BASELINE Cas12a adenine editor irreversibly edit nucleotides within 50 synthetic target sites, integrated multiple times into genome. We show that accumulates lineage-specific marks over wide range biologically relevant intervals, more than 4300 bits information model pancreatic cancer, 50X increase existing technologies. Single-cell sequencing reveals high-fidelity capture these recorders, recovering reconstructions up 40 cell divisions deep, estimated mammalian development. expect apply lineage-tracing projects development disease, especially cellular makes small, distributed systems challenging.

Язык: Английский

A comprehensive spatio-cellular map of the human hypothalamus DOI Creative Commons
John A. Tadross, Lukas Steuernagel, Georgina K.C. Dowsett

и другие.

Nature, Год журнала: 2025, Номер 639(8055), С. 708 - 716

Опубликована: Фев. 5, 2025

Abstract The hypothalamus is a brain region that plays key role in coordinating fundamental biological functions 1 . However, our understanding of the underlying cellular components and neurocircuitries have, until recently, emerged primarily from rodent studies 2,3 Here we combine single-nucleus sequencing 433,369 human hypothalamic cells with spatial transcriptomics, generating comprehensive spatio-cellular transcriptional map hypothalamus, ‘HYPOMAP’. Although conservation neuronal cell types between humans mice, as based on transcriptomic identity, generally high, there are notable exceptions. Specifically, significant disparities identity pro-opiomelanocortin neurons expression levels G-protein-coupled receptors two species carry direct implications for currently approved obesity treatments. Out 452 types, find 291 clusters significantly enriched body mass index (BMI) genome-wide association study genes. This enrichment driven by 426 ‘effector’ Rare deleterious variants six these ( MC4R , PCSK1 POMC CALCR BSN CORO1A ) associate BMI at population level, has not been linked previously to BMI. Thus, HYPOMAP provides detailed atlas context serves an important resource identify new druggable targets treating wide range conditions, including reproductive, circadian metabolic disorders.

Язык: Английский

Процитировано

8
Biomaterials and scaffolds for tissue engineering and regenerative medicine DOI Creative Commons
Yang‐Hee Kim, Sanjairaj Vijayavenkataraman, Gianluca Cidonio

и другие.

Deleted Journal, Год журнала: 2024, Номер 1(1)

Опубликована: Март 25, 2024

Abstract Methods in tissue engineering and regenerative medicine are constantly evolving to address the complex challenges of repairing damaged tissues modeling diseased organs using a library various biomaterials, cellular therapies, biofabrication techniques. The BMC Collection ‘Biomaterials scaffolds for medicine’ will host most recent advances approaches, providing comprehensive resource researchers field.

Язык: Английский

Процитировано

17
Human embryonic genetic mosaicism and its effects on development and disease DOI
Sarah M. Waldvogel, Jennifer E. Posey, Margaret A. Goodell

и другие.

Nature Reviews Genetics, Год журнала: 2024, Номер unknown

Опубликована: Апрель 11, 2024

Язык: Английский

Процитировано

14
Pharmacodynamics in paramedic practice DOI

Alfie Thain,

Carl A. Webster

Journal of Paramedic Practice, Год журнала: 2025, Номер 17(2), С. 54 - 58

Опубликована: Фев. 2, 2025

Pharmacodynamics is the study of how drugs interact with body to produce their effects, a focus on mechanisms drug action and impact physiological processes. It encompasses exploration four principal families molecular targets – enzymes, receptors, ion channels transporters examines influence these achieve therapeutic outcomes. Through an understanding pharmacodynamics, paramedics can better engage evidence base underpinning commonly used medications, enhancing ability apply pharmacological principles clinical practice effectively.

Язык: Английский

Процитировано

2
Advances in Cell‐Rich Inks for Biofabricating Living Architectures DOI
J. Almeida-Pinto, Beatriz S. Moura, Vítor M. Gaspar

и другие.

Advanced Materials, Год журнала: 2024, Номер 36(27)

Опубликована: Апрель 19, 2024

Abstract Advancing biofabrication toward manufacturing living constructs with well‐defined architectures and increasingly biologically relevant cell densities is highly desired to mimic the biofunctionality of native human tissues. The formulation tissue‐like, cell‐dense inks for remains, however, challenging at various levels bioprinting process. Promising advances have been made this goal, achieving relatively high that surpass those found in conventional platforms, pushing current boundaries closer tissue‐like densities. On focus, herein overarching challenges bioprocessing cell‐rich into clinically grade engineered tissues are discussed, as well most recent ink formulations their processing technologies highlighted. Additionally, an overview foreseen developments field provided critically discussed.

Язык: Английский

Процитировано

7
Adipocyte inflammation is the primary driver of hepatic insulin resistance in a human iPSC-based microphysiological system DOI Creative Commons
Lin Qi,

Marko Groeger,

Aditi Sharma

и другие.

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Сен. 12, 2024

Язык: Английский

Процитировано

7
Haematometabolism rewiring in atherosclerotic cardiovascular disease DOI
Laurent Yvan‐Charvet, Thibault Barouillet, Coraline Borowczyk

и другие.

Nature Reviews Cardiology, Год журнала: 2025, Номер unknown

Опубликована: Янв. 2, 2025

Язык: Английский

Процитировано

1
Eagle‐Eye Inspired Meta‐Device for Phase Imaging DOI

Junxiao Zhou,

Fanglin Tian,

Jie Hu

и другие.

Advanced Materials, Год журнала: 2024, Номер 36(32)

Опубликована: Май 31, 2024

The dual-focus vision observed in eagles' eyes is an intriguing phenomenon captivates scientists since a long time. Inspired by this natural occurrence, the authors' research introduces novel bifocal meta-device incorporating polarized camera capable of simultaneously capturing images for two different polarizations with slightly focal distances. This innovative approach facilitates concurrent acquisition underfocused and overfocused single snapshot, enabling effective extraction quantitative phase information from object using transport intensity equation. Experimental demonstrations showcase application imaging to artificial objects human embryonic kidney cells, particularly emphasizing meta-device's relevance dynamic scenarios such as laser-induced ablation cells. Moreover, it provides solution quantification during process at cellular level. Notably, proposed eagle-eye inspired (EIMPI), due its simplicity compact nature, holds promise significant applications fields endoscopy headsets, where lightweight setup essential.

Язык: Английский

Процитировано

6
Eukaryotic cell size regulation and its implications for cellular function and dysfunction DOI
Yagya Chadha, Arohi Khurana, Kurt M. Schmoller

и другие.

Physiological Reviews, Год журнала: 2024, Номер 104(4), С. 1679 - 1717

Опубликована: Июнь 20, 2024

Depending on cell type, environmental inputs, and disease, the cells in human body can have widely different sizes. In recent years, it has become clear that size is a major regulator of function. However, we are only beginning to understand how optimization function determines given cell’s optimal size. Here, review currently known control strategies eukaryotic intricate link intracellular biomolecular scaling, organelle homeostasis, cycle progression. We detail size-dependent regulation early development impact differentiation. Given importance for normal cellular physiology, must account changing conditions. describe sense stimuli, such as nutrient availability, accordingly adapt their by regulating growth Moreover, discuss correlation pathological states with misregulation long time this was considered downstream consequence dysfunction. newer studies reveal reversed causality, misregulated leading pathophysiological phenotypes senescence aging. summary, highlight important roles dysfunction, which could implications both diagnostics treatment clinic.

Язык: Английский

Процитировано

6
A size-dependent division strategy accounts for leukemia cell size heterogeneity DOI Creative Commons
Mattia Miotto,

Simone Scalise,

Marco Leonetti

и другие.

Communications Physics, Год журнала: 2024, Номер 7(1)

Опубликована: Июль 18, 2024

Abstract Heterogeneity in the size distribution of cancer cell populations is linked to drug resistance and invasiveness. However, understanding how such heterogeneity arises still damped by difficulties monitoring proliferation at typical timescales mammalian cells. Here, we show infer growth regime division strategy leukemia using live fluorescence labeling flow cytometry combination with an analytical model where rates depend on powers size. We found that dynamics Jurkat T-cells reproduced (i) a sizer-like strategy, (ii) times following Erlang (iii) fluctuations up ten percent inherited fraction division. Overall, our apparatus can be extended other types environmental conditions allowing for comprehensive characterization different cells adopt.

Язык: Английский

Процитировано

6