p65 signaling dynamics drive the developmental progression of hematopoietic stem and progenitor cells through cell cycle regulation

Clyde A. Campbell (), Rodolfo Calderon, Giulia Pavani, Xiaoyi Cheng, Radwa Barakat, Elizabeth Snella, Fang Liu, Xiyu Peng, Jeffrey J. Essner, Karin S. Dorman, Maura McGrail, Paul Gadue, Deborah L. French and Raquel Espin-Palazon ()
Additional contact information
Clyde A. Campbell: Development and Cell Biology; Iowa State University
Rodolfo Calderon: Development and Cell Biology; Iowa State University
Giulia Pavani: The Children’s Hospital of Philadelphia
Xiaoyi Cheng: Development and Cell Biology; Iowa State University
Radwa Barakat: Development and Cell Biology; Iowa State University
Elizabeth Snella: Development and Cell Biology; Iowa State University
Fang Liu: Development and Cell Biology; Iowa State University
Xiyu Peng: Iowa State University
Jeffrey J. Essner: Development and Cell Biology; Iowa State University
Karin S. Dorman: Development and Cell Biology; Iowa State University
Maura McGrail: Development and Cell Biology; Iowa State University
Paul Gadue: The Children’s Hospital of Philadelphia
Deborah L. French: The Children’s Hospital of Philadelphia
Raquel Espin-Palazon: Development and Cell Biology; Iowa State University

Nature Communications, 2024, vol. 15, issue 1, 1-22

Abstract: Abstract Most gene functions have been discovered through phenotypic observations under loss of function experiments that lack temporal control. However, cell signaling relies on limited transcriptional effectors, having to be re-used temporally and spatially within the organism. Despite that, the dynamic nature of signaling pathways have been overlooked due to the difficulty on their assessment, resulting in important bottlenecks. Here, we have utilized the rapid and synchronized developmental transitions occurring within the zebrafish embryo, in conjunction with custom NF-kB reporter embryos driving destabilized fluorophores that report signaling dynamics in real time. We reveal that NF-kB signaling works as a clock that controls the developmental progression of hematopoietic stem and progenitor cells (HSPCs) by two p65 activity waves that inhibit cell cycle. Temporal disruption of each wave results in contrasting phenotypic outcomes: loss of HSPCs due to impaired specification versus proliferative expansion and failure to delaminate from their niche. We also show functional conservation during human hematopoietic development using iPSC models. Our work identifies p65 as a previously unrecognized contributor to cell cycle regulation, revealing why and when pro-inflammatory signaling is required during HSPC development. It highlights the importance of considering and leveraging cell signaling as a temporally dynamic entity.

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

Downloads: (external link)
https://www.nature.com/articles/s41467-024-51922-5 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_s41467-024-51922-5

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

DOI: 10.1038/s41467-024-51922-5

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 ().