Identification of an embryonic differentiation stage marked by Sox1 and FoxA2 co-expression using combined cell tracking and high dimensional protein imaging.
Animals
Mice
Cell Differentiation
Hepatocyte Nuclear Factor 3-beta
/ metabolism
SOXB1 Transcription Factors
/ metabolism
Mouse Embryonic Stem Cells
/ metabolism
Gene Expression Regulation, Developmental
Cell Tracking
/ methods
Nanog Homeobox Protein
/ metabolism
Cell Lineage
Endoderm
/ metabolism
Single-Cell Analysis
/ methods
Embryonic Development
/ genetics
Neural Plate
/ metabolism
Embryo, Mammalian
/ metabolism
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
09 Sep 2024
09 Sep 2024
Historique:
received:
31
05
2023
accepted:
26
08
2024
medline:
10
9
2024
pubmed:
10
9
2024
entrez:
9
9
2024
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 39251590
doi: 10.1038/s41467-024-52069-z
pii: 10.1038/s41467-024-52069-z
doi:
Substances chimiques
Hepatocyte Nuclear Factor 3-beta
135845-92-0
Sox1 protein, mouse
0
SOXB1 Transcription Factors
0
Foxa2 protein, mouse
0
Nanog Homeobox Protein
0
Nanog protein, mouse
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
7860Informations de copyright
© 2024. The Author(s).
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