ALDH1A3-acetaldehyde re-wires neural crest stem cell and high metabolism states to potentiate melanoma heterogeneity DOI Creative Commons
Yuting Lu, Jana Trávníčková, Mihaly Badonyi

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Nov. 1, 2023

Abstract Cancer cellular heterogeneity and therapy resistance arise substantially from metabolic transcriptional adaptations, but how these are interconnected is poorly understood. Here, we show that in melanoma, the cancer stem cell marker aldehyde dehydrogenase 1A3 (ALDH1A3) forms an enzymatic partnership with acetyl-CoA synthetase 2 (ACSS2) nucleus to couple high glucose flux acetyl-histone H3 modification of neural crest lineage metabolism genes. Importantly, acetaldehyde a metabolite source for ALDH1A3, dependent manner providing physiologic function this highly volatile toxic metabolite. In zebrafish model melanoma residual disease, subpopulation ALDH1-high cells emerges following BRAF inhibitor treatment targeting ALDH1 suicide inhibitor, nifuroxazide, delays or prevents drug-resistant relapse. Our work reveals ALDH1A3-ACSS2 directly coordinates nuclear acetaldehyde-acetyl-CoA specific chromatin-based gene regulation represents potential therapeutic vulnerability melanoma. Highlights ALDH1A3-high melanomas dual state. Nuclear ALDH1A3 partners ACSS2 promote selective H3. Acetaldehyde acetyl histone acetylation. master regulator pharmaceutical target heterogeneity.

Language: Английский

The journey from melanocytes to melanoma DOI
Patricia P. Centeno, Valeria Pavet, Richard Marais

et al.

Nature reviews. Cancer, Journal Year: 2023, Volume and Issue: 23(6), P. 372 - 390

Published: April 24, 2023

Language: Английский

Citations

86
Zebrafish pigment cells develop directly from persistent highly multipotent progenitors DOI Creative Commons

Tatiana Subkhankulova,

Karen Camargo Sosa, Л. А. Урошлев

et al.

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: March 6, 2023

Abstract Neural crest cells are highly multipotent stem cells, but it remains unclear how their fate restriction to specific fates occurs. The direct model hypothesises that migrating maintain full multipotency, whilst progressive envisages fully transitioning partially-restricted intermediates before committing individual fates. Using zebrafish pigment cell development as a model, we show applying NanoString hybridization single transcriptional profiling and RNAscope in situ neural retain broad multipotency throughout migration even post-migratory vivo, with no evidence for intermediates. We find leukocyte tyrosine kinase early expression marks stage, signalling driving iridophore differentiation through repression of fate-specific transcription factors other reconcile the models by proposing occurs directly, dynamically, from state, consistent our recently-proposed Cyclical Fate Restriction model.

Language: Английский

Citations

56
Cancer drug-tolerant persister cells: from biological questions to clinical opportunities DOI
Mariangela Russo,

Mengnuo Chen,

Elisa Mariella

et al.

Nature reviews. Cancer, Journal Year: 2024, Volume and Issue: 24(10), P. 694 - 717

Published: Sept. 2, 2024

Language: Английский

Citations

15
Noncoding RNA circuitry in melanoma onset, plasticity, and therapeutic response DOI
Katerina Grafanaki, Ioannis Grammatikakis, Arin Ghosh

et al.

Pharmacology & Therapeutics, Journal Year: 2023, Volume and Issue: 248, P. 108466 - 108466

Published: June 8, 2023

Language: Английский

Citations

18
Melanocyte lineage dynamics in development, growth and disease DOI Creative Commons
Alessandro Brombin, E. Elizabeth Patton

Development, Journal Year: 2024, Volume and Issue: 151(15)

Published: Aug. 1, 2024

Melanocytes evolved to produce the melanin that gives colour our hair, eyes and skin. The melanocyte lineage also rise melanoma, most lethal form of skin cancer. differentiates from neural crest cells during development, melanocytes reside in where they are replenished by stem cells. Because molecular mechanisms necessary for specification, migration, proliferation differentiation co-opted melanoma initiation progression, studying development is directly relevant human disease. Here, through lens advances cellular omic genomic technologies, we review latest findings differentiation, how these developmental pathways become dysregulated

Language: Английский

Citations

7
Melanocyte stem cells in the skin: Origin, biological characteristics, homeostatic maintenance and therapeutic potential DOI Creative Commons
Luling Huang, Yuzhi Zuo, Shuli Li

et al.

Clinical and Translational Medicine, Journal Year: 2024, Volume and Issue: 14(5)

Published: May 1, 2024

Abstract Melanocyte stem cells (MSCs), melanocyte lineage‐specific skin derived from the neural crest, are observed in mammalian hair follicle, epidermis or sweat gland. MSCs differentiate into mature melanin‐producing melanocytes, which confer and pigmentation uphold vital functions. In controlling coordinating homeostasis, repair regeneration of tissue, play a role. Decreased numbers impaired functions closely associated with development therapy many conditions, such as graying, vitiligo, wound healing melanoma. With advancement cell technology, relevant features have been further elaborated. this review, we provide an exhaustive overview cutaneous highlight latest advances MSC research. A better understanding biological characteristics micro‐environmental regulatory mechanisms will help to improve clinical applications regenerative medicine, disorders cancer therapy. Key points This review provides concise summary origin, characteristics, homeostatic maintenance therapeutic potential MSCs. The role application value discussed. significance single‐cell RNA sequencing, CRISPR‐Cas9 technology practical models research is highlighted.

Language: Английский

Citations

6
TFAP2 paralogs facilitate chromatin access for MITF at pigmentation and cell proliferation genes DOI Creative Commons
Colin Kenny, Ramile Dilshat, Hannah Seberg

et al.

PLoS Genetics, Journal Year: 2022, Volume and Issue: 18(5), P. e1010207 - e1010207

Published: May 17, 2022

In developing melanocytes and in melanoma cells, multiple paralogs of the Activating-enhancer-binding Protein 2 family transcription factors (TFAP2) contribute to expression genes encoding pigmentation regulators, but their interaction with Microphthalmia factor (MITF), a master regulator these is unclear. Supporting model that TFAP2 facilitates MITF’s ability activate genes, single-cell seq analysis zebrafish embryos revealed are only expressed subset mitfa -expressing cells also express tfap2 paralogs. To test this SK-MEL-28 we deleted two highest expression, TFAP2A TFAP2C , creating knockout ( -KO) cells. We then assessed gene chromatin accessibility, binding MITF, marks H3K27Ac H3K27Me3 which characteristic active enhancers silenced chromatin, respectively. Integrated analyses datasets indicate directly near enriched for roles proliferation, repress cell adhesion. Consistently, compared WT -KO proliferate less adhere one another more. MITF co-operatively enhancers, former necessary accessibility. By contrast, do not appear inhibit enhancers. These studies reveal mechanism by profoundly influences set activated thereby phenotype pigment

Language: Английский

Citations

27
Revealing mitf functions and visualizing allografted tumor metastasis in colorless and immunodeficient Xenopus tropicalis DOI Creative Commons
Rensen Ran, Lanxin Li, Tingting Xu

et al.

Communications Biology, Journal Year: 2024, Volume and Issue: 7(1)

Published: March 5, 2024

Abstract Transparent immunodeficient animal models not only enhance in vivo imaging investigations of visceral organ development but also facilitate tracking transplanted tumor cells. However, at present, transparent and are confined to zebrafish, presenting substantial challenges for real-time, studies addressing specific biological inquiries. Here, we employed a mitf −/− / prkdc il2rg triple-knockout strategy establish colorless amphibian model Xenopus tropicalis . By disrupting the gene, observed loss melanophores, xanthophores, granular glands Through endogenous promoter drive BRAF V600E expression, confirmed expression xanthophores glands. Moreover, reconstruction disrupted site effectively reinstated glands, further highlighting crucial role as regulator their development. crossing frogs with frogs, generated line, providing model. Utilizing this model, successfully intravital metastases allotransplanted xanthophoromas migrations melanomas. Overall, holds great promise valuable platform tumorous developmental biology research.

Language: Английский

Citations

5
ALDH1A3-acetaldehyde metabolism potentiates transcriptional heterogeneity in melanoma DOI Creative Commons
Yuting Lu, Jana Trávníčková, Mihaly Badonyi

et al.

Cell Reports, Journal Year: 2024, Volume and Issue: 43(7), P. 114406 - 114406

Published: July 1, 2024

Language: Английский

Citations

5
Cutaneous Pigment Cell Distributions and Skin Structure of Xenopus DOI
Weizheng Liang,

C. Hou,

Zhenpeng Zhu

et al.

Pigment Cell & Melanoma Research, Journal Year: 2025, Volume and Issue: 38(3)

Published: May 1, 2025

ABSTRACT Pigment cells not only are intrinsic factors to determine animal patterns, but also play vital roles in numerous behavioral and physiological processes as well health, such melanomas originating from melanocytes. Model organisms commonly used study pigment cell development the mechanisms underlying related diseases, with zebrafish mice, Xenopus being well‐established examples. tropicalis , a diploid amphibian model, offers advantages high fecundity easily observable development. Recent advancements gene‐editing techniques have increased its prominence research on biology melanoma pathogenesis. Here, we compare skin distribution structure X. zebrafish, humans point out potential value of using model human melanoma.

Language: Английский

Citations

0