Computational simulation of JAK/STAT signaling in somatic versus germline stem cells.
Dev Dyn
; 253(7): 648-658, 2024 Jul.
Article
em En
| MEDLINE
| ID: mdl-38126664
ABSTRACT
BACKGROUND:
The Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway regulates a variety of cellular processes. A major activation event in this pathway involves the phosphorylation of a tyrosine of STAT, converting unphosphorylated STAT (uSTAT) to phosphorylated STAT (pSTAT), an active transcription factor. In a noncanonical role, uSTAT contributes to the maintenance of heterochromatin stability. As such, an increase in pSTAT concurrently reduces uSTAT, resulting in heterochromatin loss, as observed in Drosophila somatic tissues. Paradoxically, an opposing phenomenon occurs in Drosophila male germline stem cells (GSCs), where the JAK/STAT pathway remains persistently active due to a continuous supply of ligands. Here, computational simulations were employed to dissect JAK/STAT pathway activation under different cellular contexts, mimicking somatic and germline cells. In these simulations, ordinary differential equations were leveraged to replicate the chemical reactions governing JAK/STAT signaling under different conditions.RESULTS:
The outcomes indicate that transient ligand stimulation, typical in somatic tissues, led to a momentary reduction in uSTAT levels. Conversely, sustained ligand stimulation, a characteristic feature of the GSC niche, resulted in elevated uSTAT levels at equilibrium.CONCLUSION:
The simulation suggests that the duration of ligand exposure could explain the observed opposite effects of JAK/STAT activation on heterochromatin in somatic versus GSCs.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Simulação por Computador
/
Transdução de Sinais
/
Fatores de Transcrição STAT
/
Janus Quinases
/
Células Germinativas
Limite:
Animals
Idioma:
En
Revista:
Dev Dyn
Assunto da revista:
ANATOMIA
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Estados Unidos