Super-Resolution Compatible DNA Labeling Technique Reveals Chromatin Mobility and Organization Changes During Differentiation

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F25%3A00642600" target="_blank" >RIV/61388963:_____/25:00642600 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216208:11310/25:10513959

Výsledek na webu

<a href="https://doi.org/10.1002/advs.202505955" target="_blank" >https://doi.org/10.1002/advs.202505955</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1002/advs.202505955" target="_blank" >10.1002/advs.202505955</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Super-Resolution Compatible DNA Labeling Technique Reveals Chromatin Mobility and Organization Changes During Differentiation

Popis výsledku v původním jazyce

Chromatin dynamics play a crucial role in cellular differentiation, yet tools for studying global chromatin mobility in living cells remain limited. Here, a novel probe is developeded for the metabolic labeling of chromatin and tracking its mobility during neural differentiation. The labeling system utilizes a newly developed silicon rhodamine-conjugated deoxycytidine triphosphate (dCSiRTP). It is shown that this dCTP is efficiently delivered into living human induced pluripotent stem cells (iPSCs) and neural stem cells (NSCs) via a synthetic transporter (SNTT1). Using correlative confocal microscopy and stimulated emission depletion (STED) super-resolution microscopy, the sizes of labeled chromatin domains are quantified. Time-lapse super-resolution microscopy combined with single particle tracking revealed that chromatin mobility decreases during the transition from iPSCs (pluripotent state) to NSCs and neurons (differentiated state). This reduction in mobility correlates with the differentiation state, reflecting changes in chromatin organization during cell fate commitment. Concomitant mechanistic insights obtained from micrococcal nuclease digestion assays, chromatin compaction, and histone modification analyses revealed a decrease in chromatin accessibility during neuronal differentiation. These data indicate that chromatin adopts a more constrained structure with reduced accessibility and increased heterochromatin-associated histone modifications. These findings provide new insights into chromatin regulation during neurogenesis.

Název v anglickém jazyce

Super-Resolution Compatible DNA Labeling Technique Reveals Chromatin Mobility and Organization Changes During Differentiation

Popis výsledku anglicky

Chromatin dynamics play a crucial role in cellular differentiation, yet tools for studying global chromatin mobility in living cells remain limited. Here, a novel probe is developeded for the metabolic labeling of chromatin and tracking its mobility during neural differentiation. The labeling system utilizes a newly developed silicon rhodamine-conjugated deoxycytidine triphosphate (dCSiRTP). It is shown that this dCTP is efficiently delivered into living human induced pluripotent stem cells (iPSCs) and neural stem cells (NSCs) via a synthetic transporter (SNTT1). Using correlative confocal microscopy and stimulated emission depletion (STED) super-resolution microscopy, the sizes of labeled chromatin domains are quantified. Time-lapse super-resolution microscopy combined with single particle tracking revealed that chromatin mobility decreases during the transition from iPSCs (pluripotent state) to NSCs and neurons (differentiated state). This reduction in mobility correlates with the differentiation state, reflecting changes in chromatin organization during cell fate commitment. Concomitant mechanistic insights obtained from micrococcal nuclease digestion assays, chromatin compaction, and histone modification analyses revealed a decrease in chromatin accessibility during neuronal differentiation. These data indicate that chromatin adopts a more constrained structure with reduced accessibility and increased heterochromatin-associated histone modifications. These findings provide new insights into chromatin regulation during neurogenesis.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10608 - Biochemistry and molecular biology

Projekt

<a href="/cs/project/GX20-00885X" target="_blank" >GX20-00885X: Nové funkcionalizované (bio)polymery na bázi dekorace DNA malými molekulami</a><br>

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2025

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Advanced Science

ISSN

2198-3844

e-ISSN

2198-3844

Svazek periodika

12

Číslo periodika v rámci svazku

45

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

15

Strana od-do

e05955

Kód UT WoS článku

001566389700001

EID výsledku v databázi Scopus

2-s2.0-105015576873