Phosphatidylinositol-3 kinase signaling controls survival and stemness of hematopoietic stem and progenitor cells
| Autor: | Stefan Schulte-Merker, Sasja Blokzijl-Franke, Philippe Herbomel, Jeroen den Hertog, Karima Kissa, Bas Ponsioen, Suma Choorapoikayil |
|---|---|
| Přispěvatelé: | Hubrecht Institute for Developmental Biology and Stem Cell Research |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Cancer Research Biology Article 03 medical and health sciences Dorsal aorta Phosphatidylinositol 3-Kinases 0302 clinical medicine Downregulation and upregulation Genetics PTEN Hematopoietic Stem Cells/metabolism Animals Humans Progenitor cell Molecular Biology PI3K/AKT/mTOR pathway Zebrafish Stem Cells/metabolism Stem Cells Hematopoietic Tissue Hematopoietic Stem Cells Survival Analysis Cell biology Haematopoiesis 030104 developmental biology biology.protein Phosphatidylinositol 3-kinase signaling Female Phosphatidylinositol 3-Kinases/metabolism 030217 neurology & neurosurgery Cell signalling Signal Transduction |
| Zdroj: | Oncogene Oncogene, 40(15), 2741-2755. Nature Publishing Group |
| ISSN: | 1476-5594 0950-9232 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full text from SpringerLink