Tropomyosin 1 genetically constrains in vitro hematopoiesis.
BMC Biol
; 18(1): 52, 2020 05 14.
Article
en En
| MEDLINE
| ID: mdl-32408895
ABSTRACT
BACKGROUND:
Identifying causal variants and genes from human genetic studies of hematopoietic traits is important to enumerate basic regulatory mechanisms underlying these traits, and could ultimately augment translational efforts to generate platelets and/or red blood cells in vitro. To identify putative causal genes from these data, we performed computational modeling using available genome-wide association datasets for platelet and red blood cell traits.RESULTS:
Our model identified a joint collection of genomic features enriched at established trait associations and plausible candidate variants. Additional studies associating variation at these loci with change in gene expression highlighted Tropomyosin 1 (TPM1) among our top-ranked candidate genes. CRISPR/Cas9-mediated TPM1 knockout in human induced pluripotent stem cells (iPSCs) enhanced hematopoietic progenitor development, increasing total megakaryocyte and erythroid cell yields.CONCLUSIONS:
Our findings may help explain human genetic associations and identify a novel genetic strategy to enhance in vitro hematopoiesis. A similar trait-specific gene prioritization strategy could be employed to help streamline functional validation experiments for virtually any human trait.Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Tropomiosina
/
Plaquetas
/
Células Madre Hematopoyéticas
/
Hematopoyesis
Límite:
Humans
Idioma:
En
Revista:
BMC Biol
Asunto de la revista:
BIOLOGIA
Año:
2020
Tipo del documento:
Article
País de afiliación:
Estados Unidos