Single-cell omics identifies inflammatory signaling as a trans-differentiation trigger in mouse embryos

Copyright © 2024 Elsevier Inc. All rights reserved..

Trans-differentiation represents a direct lineage conversion; however, insufficient characterization of this process hinders its potential applications. Here, to explore a potential universal principal for trans-differentiation, we performed single-cell transcriptomic analysis of endothelial-to-hematopoietic transition (EHT), endothelial-to-mesenchymal transition, and epithelial-to-mesenchymal transition in mouse embryos. We applied three scoring indexes of entropies, cell-type signature transcription factor expression, and critical transition signals to show common features underpinning the fate plasticity of transition states. Cross-model comparison identified inflammatory-featured transition states and a common trigger role of interleukin-33 in promoting fate conversions. Multimodal profiling (integrative transcriptomic and chromatin accessibility analysis) demonstrated the inflammatory regulation of hematopoietic specification. Furthermore, multimodal omics and fate-mapping analyses showed that endothelium-specific Spi1, as an inflammatory effector, governs appropriate chromatin accessibility and transcriptional programs to safeguard EHT. Overall, our study employs single-cell omics to identify critical transition states/signals and the common trigger role of inflammatory signaling in developmental-stress-induced fate conversions.

Medienart:

E-Artikel

Erscheinungsjahr:

2024

Erschienen:

2024

Enthalten in:

Zur Gesamtaufnahme - volume:59

Enthalten in:

Developmental cell - 59(2024), 8 vom: 22. Apr., Seite 961-978.e7

Sprache:

Englisch

Beteiligte Personen:

Zhang, Yifan [VerfasserIn]
Kang, Zhixin [VerfasserIn]
Liu, Mengyao [VerfasserIn]
Wang, Lu [VerfasserIn]
Liu, Feng [VerfasserIn]

Links:

Volltext

Themen:

Endothelial-to-hematopoietic transition
Endothelial-to-mesenchymal transition
Epithelial-to-mesenchymal transition
Inflammatory signaling
Journal Article
Research Support, Non-U.S. Gov't
Single-cell omics
Spi1
Trans-differentiation

Anmerkungen:

Date Completed 24.04.2024

Date Revised 24.04.2024

published: Print-Electronic

Citation Status MEDLINE

doi:

10.1016/j.devcel.2024.02.010

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM369977653