Prep1 (pKnox1) regulates mouse embryonic HSC cycling and self-renewal affecting the Stat1-Sca1 IFN-dependent pathway
Autor: | Annalisa D’Avola, Livia Modica, Francesco Blasi, Giorgio Antonio Iotti |
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Jazyk: | angličtina |
Rok vydání: | 2014 |
Předmět: |
Hematopoietic Progenitor Cells
medicine.medical_treatment Science Apoptosis Smad Proteins Hematopoietic stem cell transplantation Biology Animal Cells Cell Self Renewal medicine Animals Clonogenic assay Ataxin-1 Cells Cultured Homeodomain Proteins Multidisciplinary Base Sequence Stem Cells Hematopoietic Stem Cell Transplantation Biology and Life Sciences Cell Biology Hematopoietic Stem Cells Phenotype Embryonic stem cell Cell biology Mice Inbred C57BL Haematopoiesis STAT1 Transcription Factor Liver Medicine Interferons Stem cell Signal transduction Cellular Types Signal Transduction Research Article |
Zdroj: | PLoS ONE, Vol 9, Iss 9, p e107916 (2014) PLoS ONE |
ISSN: | 1932-6203 |
Popis: | A hypomorphic Prep1 mutation results in embryonic lethality at late gestation with a pleiotropic embryonic phenotype that includes defects in all hematopoietic lineages. Reduced functionality of the hematopoietic stem cells (HSCs) compartment might be responsible for the hematopoietic phenotype observed at mid-gestation. In this paper we demonstrate that Prep1 regulates the number of HSCs in fetal livers (FLs), their clonogenic potential and their ability to de novo generate the hematopoietic system in ablated hosts. Furthermore, we show that Prep1 controls the self-renewal ability of the FL HSC compartment as demonstrated by serial transplantation experiments. The premature exhaustion of Prep1 mutant HSCs correlates with the reduced quiescent stem cell pool thus suggesting that Prep1 regulates the self-renewal ability by controlling the quiescence/proliferation balance. Finally, we show that in FL HSCs Prep1 absence induces the interferon signaling pathway leading to premature cycling and exhaustion of fetal HSCs. |
Databáze: | OpenAIRE |
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