Evidence map›Paper›PMID 41803112›Full record

ArticleNature communications2026

FLEXTAG: a small and self-renewable protein labeling system for anti-fading multi-color super-resolution imaging.

Han Zhang, Yuan Yao, Xuye Wang, Yuanmin Zheng, Shaoqing Zhang, Yuan Tao, Haopeng Yang, Yinqi Wang, Mengde Liu, Marina Feric and 1 more

Abstract read
In one paragraph

Article in Nature communications, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Review
  2. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

11 authors.

Han ZhangDepartment of Chemistry, The Pennsylvania State University, University Park, PA, USA.ORCID 0009-0007-0111-5351
Yuan YaoDepartment of Chemistry, The Pennsylvania State University, University Park, PA, USA.
Xuye WangDepartment of Chemistry, The Pennsylvania State University, University Park, PA, USA.
Yuanmin ZhengDepartment of Chemistry, The Pennsylvania State University, University Park, PA, USA.ORCID 0000-0001-6620-3634
Shaoqing ZhangDepartment of Chemistry, The Pennsylvania State University, University Park, PA, USA.
Yuan TaoDepartment of Chemistry, The Pennsylvania State University, University Park, PA, USA.ORCID 0000-0002-6026-9584
Haopeng YangDepartment of Chemistry, The Pennsylvania State University, University Park, PA, USA.
Yinqi WangDepartment of Chemistry, The Pennsylvania State University, University Park, PA, USA.
Mengde LiuDepartment of Chemistry, The Pennsylvania State University, University Park, PA, USA.
Marina FericDepartment of Chemistry, The Pennsylvania State University, University Park, PA, USA.ORCID 0000-0001-7531-9305
Ruobo ZhouDepartment of Chemistry, The Pennsylvania State University, University Park, PA, USA. ruobo.zhou@psu.edu.ORCID 0000-0001-8628-0282

Funding

Deciphering the functional role of actin-spectrin-based membrane skeleton in subcellular compartmentalization of signaling proteins and cell signal transductionR35GM142973 · NIGMS · PENNSYLVANIA STATE UNIVERSITY, THE · PI ZHOU, RUOBO · 2021 to 2025
$2.2M
Flow Of Gene Expression Across Mitochondrial CondensatesR35GM154931 · NIGMS · PENNSYLVANIA STATE UNIVERSITY, THE · PI Marina Feric · 2024 to 2026
$1.2M
NIGMS NIH HHS R35 GM142973NIGMS NIH HHS R35 GM154931U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS) R35GM142973
6 · The paper itself

Abstract

Super-resolution fluorescence imaging enables visualization of subcellular structures and molecular interactions at the nanoscale, but its broader application has been hindered by long-standing limitations in current protein tagging systems, including rapid photobleaching, tag-induced artifacts, poor post-fixation labeling efficiency, and restricted multiplexing capability. Here, we present FLEXTAG (Fluorescent Labeling for Exchangeable, X-resilient Tagging in Advanced Generic Nanoscopy), a comprehensive protein labeling system comprising three orthogonal, ultrasmall (12-18 kDa), and self-renewable protein tags that collectively overcome these major limitations of existing tagging systems, enabling optimized multi-color super-resolution imaging. Through continuous exchange of organic fluorophores, FLEXTAG supports extended durations of high-resolution imaging in both live and fixed cells with minimal photobleaching. It is compatible with major super-resolution modalities, such as SIM, STED, STORM, and PAINT, and is applicable to a wide range of subcellular targets. To further address fixation-induced labeling inefficiency and background fluorescence, we developed an innovative protection-based fixation method and chemical blocking strategies that significantly preserve tag accessibility and enhance signal-to-noise ratio, improvements that are broadly applicable to other protein tagging systems. Altogether, FLEXTAG enables long-term tracking of dynamic behaviors and interactions of subcellular targets, as well as mapping of nanoscale protein organizations and cellular architecture, advancing both basic research and translational applications in cell biology.

Indexed as

Fluorescent DyesProteinsStaining and LabelingAnimalsHeLa CellsHumansMicroscopy, FluorescencePhotobleachingFluorescent DyesProteins

Identifiers

PMID41803112
PMCPMC12972069

What OpenQuestion holds

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LicenceCC BY-NC-ND
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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.