Identification of an embryonic differentiation stage marked by Sox1 and FoxA2 co-expression using combined cell tracking and high dimensional protein imaging.
Nat Commun
; 15(1): 7860, 2024 Sep 09.
Article
em En
| MEDLINE
| ID: mdl-39251590
ABSTRACT
Pluripotent mouse embryonic stem cells (ESCs) can differentiate to all germ layers and serve as an in vitro model of embryonic development. To better understand the differentiation paths traversed by ESCs committing to different lineages, we track individual differentiating ESCs by timelapse imaging followed by multiplexed high-dimensional Imaging Mass Cytometry (IMC) protein quantification. This links continuous live single-cell molecular NANOG and cellular dynamics quantification over 5-6 generations to protein expression of 37 different molecular regulators in the same single cells at the observation endpoints. Using this unique data set including kinship history and live lineage marker detection, we show that NANOG downregulation occurs generations prior to, but is not sufficient for neuroectoderm marker Sox1 upregulation. We identify a developmental cell type co-expressing both the canonical Sox1 neuroectoderm and FoxA2 endoderm markers in vitro and confirm the presence of such a population in the post-implantation embryo. RNASeq reveals cells co-expressing SOX1 and FOXA2 to have a unique cell state characterized by expression of both endoderm as well as neuroectoderm genes suggesting lineage potential towards both germ layers.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Diferenciação Celular
/
Regulação da Expressão Gênica no Desenvolvimento
/
Fator 3-beta Nuclear de Hepatócito
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Fatores de Transcrição SOXB1
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Células-Tronco Embrionárias Murinas
Limite:
Animals
Idioma:
En
Revista:
Nat Commun
Assunto da revista:
BIOLOGIA
/
CIENCIA
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Suíça
País de publicação:
Reino Unido