Genetic Instruction of Megakaryocytes and Platelets Derived from Human Induced Pluripotent Stem Cells for Studies of Integrin Regulation.
Methods Mol Biol
; 2217: 237-249, 2021.
Article
en En
| MEDLINE
| ID: mdl-33215384
ABSTRACT
Platelets are small, anucleate cells that play oversized roles in hemostasis, immunity, and inflammation. An important mediator of platelet function is integrin αIIbß3, which is required for fibrinogen-dependent platelet aggregation during hemostasis. This platelet response is dependent on conformational changes in the integrin induced by "inside-out" biochemical signals that are triggered by platelet agonists. In turn, fibrinogen binding to αIIbß3 initiates "outside-in" biochemical and mechanical signals that regulate the platelet cytoskeleton and help to promote full platelet aggregation and secretory responses. Without a nucleus, there is a limited range of experimental manipulations that are possible with human platelets to study the molecular basis of integrin signaling in these primary cells. Consequently, many studies of αIIbß3 function use genetic approaches that rely on heterologous expression systems or platelets from gene-targeted mice, sometimes with uncertain applicability to human platelets. This chapter will detail a method for genetic manipulation of megakaryocytes and platelets derived from human induced pluripotent stem cells for molecular studies of αIIbß3 signaling and for modeling of human platelet functions potentially relevant to hemostasis, immunity, and inflammation.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Plaquetas
/
Megacariocitos
/
Agregación Plaquetaria
/
Complejo GPIIb-IIIa de Glicoproteína Plaquetaria
/
Complejo GPIb-IX de Glicoproteína Plaquetaria
/
Glicoproteína IIb de Membrana Plaquetaria
/
Ingeniería Celular
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
Methods Mol Biol
Asunto de la revista:
BIOLOGIA MOLECULAR
Año:
2021
Tipo del documento:
Article
País de afiliación:
Estados Unidos