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p65 signaling dynamics drive the developmental progression of hematopoietic stem and progenitor cells through cell cycle regulation.
Campbell, Clyde A; Calderon, Rodolfo; Pavani, Giulia; Cheng, Xiaoyi; Barakat, Radwa; Snella, Elizabeth; Liu, Fang; Peng, Xiyu; Essner, Jeffrey J; Dorman, Karin S; McGrail, Maura; Gadue, Paul; French, Deborah L; Espin-Palazon, Raquel.
Afiliação
  • Campbell CA; Department of Genetics, Development and Cell Biology; Iowa State University, Ames, IA, 50011, USA. clyde@iastate.edu.
  • Calderon R; Department of Genetics, Development and Cell Biology; Iowa State University, Ames, IA, 50011, USA.
  • Pavani G; Center for Cellular and Molecular Therapeutics, The Children's Hospital of Philadelphia, Philadelphia, PA, USA.
  • Cheng X; Department of Genetics, Development and Cell Biology; Iowa State University, Ames, IA, 50011, USA.
  • Barakat R; Department of Genetics, Development and Cell Biology; Iowa State University, Ames, IA, 50011, USA.
  • Snella E; Department of Toxicology, Faculty of Veterinary Medicine, Benha University, Qalyubia, 13518, Egypt.
  • Liu F; Department of Genetics, Development and Cell Biology; Iowa State University, Ames, IA, 50011, USA.
  • Peng X; Department of Genetics, Development and Cell Biology; Iowa State University, Ames, IA, 50011, USA.
  • Essner JJ; Department of Statistics, Iowa State University, Ames, IA, 50011, USA.
  • Dorman KS; Department of Genetics, Development and Cell Biology; Iowa State University, Ames, IA, 50011, USA.
  • McGrail M; Department of Genetics, Development and Cell Biology; Iowa State University, Ames, IA, 50011, USA.
  • Gadue P; Department of Statistics, Iowa State University, Ames, IA, 50011, USA.
  • French DL; Department of Genetics, Development and Cell Biology; Iowa State University, Ames, IA, 50011, USA.
  • Espin-Palazon R; Center for Cellular and Molecular Therapeutics, The Children's Hospital of Philadelphia, Philadelphia, PA, USA.
Nat Commun ; 15(1): 7787, 2024 Sep 06.
Article em En | MEDLINE | ID: mdl-39242546
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.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Peixe-Zebra / Células-Tronco Hematopoéticas / Transdução de Sinais / Ciclo Celular Limite: Animals / Humans Idioma: En Revista: Nat Commun Ano de publicação: 2024 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Peixe-Zebra / Células-Tronco Hematopoéticas / Transdução de Sinais / Ciclo Celular Limite: Animals / Humans Idioma: En Revista: Nat Commun Ano de publicação: 2024 Tipo de documento: Article