PUBLICATION

Phosphatidylinositol-3 kinase signaling controls survival and stemness of hematopoietic stem and progenitor cells

Authors
Blokzijl-Franke, S., Ponsioen, B., Schulte-Merker, S., Herbomel, P., Kissa, K., Choorapoikayil, S., den Hertog, J.
ID
ZDB-PUB-210316-6
Date
2021
Source
Oncogene   40(15): 2741-2755 (Journal)
Registered Authors
den Hertog, Jeroen, Herbomel, Philippe, Schulte-Merker, Stefan
Keywords
none
Datasets
GEO:GSE166900
MeSH Terms
  • Animals
  • Female
  • Hematopoietic Stem Cells/metabolism*
  • Humans
  • Phosphatidylinositol 3-Kinases/metabolism*
  • Signal Transduction
  • Stem Cells/metabolism*
  • Survival Analysis
  • Zebrafish
PubMed
33714985 Full text @ Oncogene
Abstract
Hematopoietic stem and progenitor cells (HSPCs) are multipotent cells giving rise to all blood lineages during life. HSPCs emerge from the ventral wall of the dorsal aorta (VDA) during a specific timespan in embryonic development through endothelial hematopoietic transition (EHT). We investigated the ontogeny of HSPCs in mutant zebrafish embryos lacking functional pten, an important tumor suppressor with a central role in cell signaling. Through in vivo live imaging, we discovered that in pten mutant embryos a proportion of the HSPCs died upon emergence from the VDA, an effect rescued by inhibition of phosphatidylinositol-3 kinase (PI3K). Surprisingly, inhibition of PI3K in wild-type embryos also induced HSPC death. Surviving HSPCs colonized the caudal hematopoietic tissue (CHT) normally and committed to all blood lineages. Single-cell RNA sequencing indicated that inhibition of PI3K enhanced survival of multipotent progenitors, whereas the number of HSPCs with more stem-like properties was reduced. At the end of the definitive wave, loss of Pten caused a shift to more restricted progenitors at the expense of HSPCs. We conclude that PI3K signaling tightly controls HSPCs survival and both up- and downregulation of PI3K signaling reduces stemness of HSPCs.
Genes / Markers
Figures
Figure Gallery
Expression
Phenotype
Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping
Errata and Notes