Cited by 214Single-cell and spatial transcriptomicsDevelopmental Biology and Gene RegulationPluripotent Stem Cells Research

A single-embryo, single-cell time-resolved model for mouse gastrulation

Open access
Mittnenzweig, Markus, Mayshar, Yoav, Cheng, Saifeng, Ben-Yair, Raz, Hadas, Ron, Rais, Yoach, Chomsky, Elad, Reines, Netta +7 more·2021·Cell

Abstract

Mouse embryonic development is a canonical model system for studying mammalian cell fate acquisition. Recently, single-cell atlases comprehensively charted embryonic transcriptional landscapes, yet inference of the coordinated dynamics of cells over such atlases remains challenging. Here, we introduce a temporal model for mouse gastrulation, consisting of data from 153 individually sampled embryos spanning 36 h of molecular diversification. Using algorithms and precise timing, we infer differentiation flows and lineage specification dynamics over the embryonic transcriptional manifold. Rapid transcriptional bifurcations characterize the commitment of early specialized node and blood cells. However, for most lineages, we observe combinatorial multi-furcation dynamics rather than hierarchical transcriptional transitions. In the mesoderm, dozens of transcription factors combinatorially regulate multifurcations, as we exemplify using time-matched chimeric embryos of Foxc1/Foxc2 mutants. Our study rejects the notion of differentiation being governed by a series of binary choices, providing an alternative quantitative model for cell fate acquisition.

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Crossref · 10.1016/j.cell.2021.04.004

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  • Cell fate choice involves a more distributed form of control relying on combinatorial activities of dozens of TFs rather than an organization strictly dominated by a few master TFs.

    “recent insights into the understanding of cell fate choice, which have suggested a more distributed form of control relying on combinatorial activities of dozens of TFs rather than an organization strictly dominated by a few master TFs (Chubb et al, 2021; Mittnenzweig et al, 2021).”

    From An extended transcription factor regulatory network controls hepatocyte identity (2023) · cites this paper as Mittnenzweig et al, 2021

    The Results section, “Evidence for combinatorial regulation of mesodermal multifurcation,” supports combinatorial involvement of many TFs in mouse mesodermal fate transitions and analyzes 63 variably expressed TFs. It also allows that master-regulator cascades can drive differentiation of specialized cell types. The claim extends the mesoderm finding to cell fate choice generally and treats dozens of TFs as active regulators, which the analysis does not establish. (LLM, conf=0.83)

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1 of the 70 references couldn’t be matched to a known paper.

Research works printed but not linked: 1

  1. Bellomo D. Lander A. Harragan I. Brown N.A. Cell proliferation in mammalian gastrulation: the ventral node and notochord are relatively quiescent Dev. Dyn. 205 1996 471 485 8901057

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Authors
Mittnenzweig, M., Mayshar, Y., Cheng, S., Ben-Yair, R., Hadas, R., Rais, Y., Chomsky, E., Reines, N., Uzonyi, A., Lumerman, L., Lifshitz, A., Mukamel, Z., Orenbuch, A.-H., Tanay, A., & Stelzer, Y.
Affiliations
Weizmann Institute of Science (IL)
Corresponding author
  • Tanay, Amos
  • Stelzer, Yonatan
Venue
Cell
Publisher
Elsevier BV
Published
2021-05
Volume
184
Issue
11
Pages
2825-2842.e22
ISSN
0092-8674 (ISSN-L)
OpenAlex
W3159883015
Cited by
214
References
70
Citations by year
2026: 33 · 2025: 39 · 2024: 52 · 2023: 40 · 2022: 37 · 2021: 12 · 2020: 1
FWCI
11.07
Type
journal article
Language
en
Open access
Locations
  • Cell (publishedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • MDC Repository (Max-Delbrueck-Center for Molecular Medicine) (acceptedVersion)
Funders
  • ERC
  • Weizmann Institute of Science
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Single-cell and spatial transcriptomics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
Keywords
mouse gastrulation, single-cell transcriptomics, lineage specification, mesoderm differentiation, FOXC1, FOXC2, chimeric embryos, embryonic development
MeSH terms
Mouse Embryonic Stem Cells, Animals, Cell Differentiation, Embryo, Mammalian, Female, Mice, Inbred C57BL, Pregnancy, Gene Expression, Sequence Analysis, RNA, Cell Lineage, Embryonic Development, Mice, Gastrulation, Single-Cell Analysis

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