Histone modification profiling reveals differential signatures associated with human embryonic stem cell self-renewal and differentiation.
Proteomics
; 16(3): 448-58, 2016 Feb.
Article
en En
| MEDLINE
| ID: mdl-26631989
ABSTRACT
In this study, we trace developmental stages using epigenome changes in human embryonic stem cells (hESCs) treated with drugs modulating either self-renewal or differentiation. Based on microscopy, qPCR and flow cytometry, we classified the treatment outcome as inducing pluripotency (hESC, flurbiprofen and gatifloxacin), mesendoderm (sinomenine), differentiation (cyamarin, digoxin, digitoxin, selegeline and theanine) and lineage-commitment (RA). When we analyzed histone PTMs that imprinted these gene and protein expressions, the above classification was reassorted. Hyperacetylation at H3K4, 9, 14, 18, 56 and 122 as well as H4K5, 8, 12 and 16 emerged as the pluripotency signature of hESCs. Methylations especially of H3 at K9, K20, K27 and K36 characterized differentiation initiation as seen in no-drug control and fluribiprofen. Sinomenine-treated cells clustered close to "differentiation initiators", consistent with flow cytometry where it induced mesendoderm, along with cyamarin and possibly selegnine. Neurectoderm, induced by RA and theanine manifested methylations on H3 shifts to H3.3. By both flow cytometry and histone PTM clustering, it appears that cells treated with gatifloxacin, flurbiprofen, digitoxin and digoxin were not yet lineage-committed or mixed cell types. Taken together, our moderate-throughput histone PTM profiling approach highlighted subtle epigenetic signatures that permitted us to predict divergent lineage progression even in differentiating cells with similar phenotype and gene expression.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Histonas
/
Procesamiento Proteico-Postraduccional
/
Linaje de la Célula
/
Epigénesis Genética
/
Células Madre Embrionarias Humanas
Tipo de estudio:
Prognostic_studies
/
Risk_factors_studies
Límite:
Humans
Idioma:
En
Revista:
Proteomics
Asunto de la revista:
BIOQUIMICA
Año:
2016
Tipo del documento:
Article
País de afiliación:
Estados Unidos