Reconstructing axial progenitor field dynamics in mouse stem cell-derived embryoids.

Autor:	Bolondi A; Department of Genome Regulation, Max Planck Institute for Molecular Genetics, 14195 Berlin, Germany., Law BK; Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ 08544, USA; Department of Molecular Biology, Princeton University, Princeton, NJ 08544, USA., Kretzmer H; Department of Genome Regulation, Max Planck Institute for Molecular Genetics, 14195 Berlin, Germany., Gassaloglu SI; Department of Genome Regulation, Max Planck Institute for Molecular Genetics, 14195 Berlin, Germany; Max Planck Institute of Molecular Cell Biology and Genetics, 01307 Dresden, Germany., Buschow R; Microscopy Core Facility, Max Planck Institute for Molecular Genetics, 14195 Berlin, Germany., Riemenschneider C; Department of Genome Regulation, Max Planck Institute for Molecular Genetics, 14195 Berlin, Germany., Yang D; Department of Molecular Pharmacology and Therapeutics & Systems Biology, Columbia University, New York, NY 10032, USA., Walther M; Department of Genome Regulation, Max Planck Institute for Molecular Genetics, 14195 Berlin, Germany., Veenvliet JV; Max Planck Institute of Molecular Cell Biology and Genetics, 01307 Dresden, Germany; Cluster of Excellence Physics of Life, Technische Universität Dresden, 01307 Dresden, Germany; Center for Systems Biology Dresden, 01307 Dresden, Germany., Meissner A; Department of Genome Regulation, Max Planck Institute for Molecular Genetics, 14195 Berlin, Germany; Institute of Chemistry and Biochemistry, Freie Universität Berlin, 14195 Berlin, Germany. Electronic address: meissner@molgen.mpg.de., Smith ZD; Department of Genetics, Yale Stem Cell Center, Yale School of Medicine, New Haven, CT 06519, USA. Electronic address: z.smith@yale.edu., Chan MM; Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ 08544, USA; Department of Molecular Biology, Princeton University, Princeton, NJ 08544, USA. Electronic address: mmchan@princeton.edu.
Jazyk:	angličtina
Zdroj:	Developmental cell [Dev Cell] 2024 Jun 17; Vol. 59 (12), pp. 1489-1505.e14. Date of Electronic Publication: 2024 Apr 04.
DOI:	10.1016/j.devcel.2024.03.024
Abstrakt:	Embryogenesis requires substantial coordination to translate genetic programs to the collective behavior of differentiating cells, but understanding how cellular decisions control tissue morphology remains conceptually and technically challenging. Here, we combine continuous Cas9-based molecular recording with a mouse embryonic stem cell-based model of the embryonic trunk to build single-cell phylogenies that describe the behavior of transient, multipotent neuro-mesodermal progenitors (NMPs) as they commit into neural and somitic cell types. We find that NMPs show subtle transcriptional signatures related to their recent differentiation and contribute to downstream lineages through a surprisingly broad distribution of individual fate outcomes. Although decision-making can be heavily influenced by environmental cues to induce morphological phenotypes, axial progenitors intrinsically mature over developmental time to favor the neural lineage. Using these data, we present an experimental and analytical framework for exploring the non-homeostatic dynamics of transient progenitor populations as they shape complex tissues during critical developmental windows. Competing Interests: Declaration of interests Z.D.S. and A.M. are co-founders and scientific advisors of Harbinger Health. D.Y. is a co-founder of and scientific advisor for DEM Biopharma. (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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