Lineage specific transcription factor waves reprogram neuroblastoma from self-renewal to differentiation

Deblina Banerjee (), Sukriti Bagchi, Zhihui Liu, Hsien-Chao Chou, Man Xu, Ming Sun, Sara Aloisi, Zalman Vaksman, Sharon J. Diskin, Mark Zimmerman, Javed Khan, Berkley Gryder () and Carol J. Thiele ()
Additional contact information
Deblina Banerjee: National Cancer Institute
Sukriti Bagchi: National Cancer Institute
Zhihui Liu: National Cancer Institute
Hsien-Chao Chou: National Cancer Institute
Man Xu: National Cancer Institute
Ming Sun: National Cancer Institute
Sara Aloisi: Case Western Reserve University
Zalman Vaksman: New York Genome Center
Sharon J. Diskin: Perelman School of Medicine
Mark Zimmerman: Dana-Farber Cancer Institute
Javed Khan: National Cancer Institute
Berkley Gryder: Case Western Reserve University
Carol J. Thiele: National Cancer Institute

Nature Communications, 2024, vol. 15, issue 1, 1-18

Abstract: Abstract Temporal regulation of super-enhancer (SE) driven transcription factors (TFs) underlies normal developmental programs. Neuroblastoma (NB) arises from an inability of sympathoadrenal progenitors to exit a self-renewal program and terminally differentiate. To identify SEs driving TF regulators, we use all-trans retinoic acid (ATRA) to induce NB growth arrest and differentiation. Time-course H3K27ac ChIP-seq and RNA-seq reveal ATRA coordinated SE waves. SEs that decrease with ATRA link to stem cell development (MYCN, GATA3, SOX11). CRISPR-Cas9 and siRNA verify SOX11 dependency, in vitro and in vivo. Silencing the SOX11 SE using dCAS9-KRAB decreases SOX11 mRNA and inhibits cell growth. Other TFs activate in sequential waves at 2, 4 and 8 days of ATRA treatment that regulate neural development (GATA2 and SOX4). Silencing the gained SOX4 SE using dCAS9-KRAB decreases SOX4 expression and attenuates ATRA-induced differentiation genes. Our study identifies oncogenic lineage drivers of NB self-renewal and TFs critical for implementing a differentiation program.

Date: 2024
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-024-47166-y Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-47166-y

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-024-47166-y

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().