Dataset Information

Molecular architecture of lineage specification and tissue organization in early mouse embryo

ABSTRACT: During postimplantation development of the mouse embryo descendants of the inner cell mass cells in the early epiblast transit from the naïve pluripotent state to the primed pluripotent state 1. Concurrent with the transition of the pluripotency states is the specification of cell lineages and formation of germ layers in the embryos that serves as the blueprint for embryogenesis. Fate mapping and lineage analysis studies have revealed that cells in different regions of the germ layers acquire location-specific cell fates during gastrulation 2–5. The regionalization of cell fates heralding the formation of the basic body plan is conserved in vertebrate embryos at a common phylotypic stage of development 6–8. Knowledge of the molecular regulation that underpin the lineage specification and tissue patterning is instrumental for understanding embryonic programming and stem cell-based translational study. However a genome-wide molecular annotation of lineage segregation and tissue architecture of post-implantation embryo has yet to be undertaken. Here we reported a spatially resolved transcriptome of cell populations at defined positions in the germ layers over the period of pre- to late gastrulation development. This spatio-temporal transcriptome provides high resolution digitized gene expression profiles and defines the molecular attribute of the genealogy of lineages and continuum of pluripotency states in time and space. The transcriptome further identifies the networks of molecular determinants that drive lineage specification and tissue patterning in the early postimplantation mouse embryo.

OTHER RELATED OMICS DATASETS IN: GSE120963

TISSUE(S): Embryos

SUBMITTER: Guangdun,Peng

PROVIDER: OEX001696 | NODE |

REPOSITORIES: NODE

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Molecular architecture of lineage allocation and tissue organization in early mouse embryo.

Peng Guangdun G Suo Shengbao S Cui Guizhong G Yu Fang F Wang Ran R Chen Jun J Chen Shirui S Liu Zhiwen Z Chen Guoyu G Qian Yun Y Tam Patrick P L PPL Han Jing-Dong J JJ Jing Naihe N

Nature 20190807 7770

During post-implantation development of the mouse embryo, descendants of the inner cell mass in the early epiblast transit from the naive to primed pluripotent state<sup>1</sup>. Concurrently, germ layers are formed and cell lineages are specified, leading to the establishment of the blueprint for embryogenesis. Fate-mapping and lineage-analysis studies have revealed that cells in different regions of the germ layers acquire location-specific cell fates during gastrulation<sup>2-5</sup>. The reg ...[more]

PMID: 31391582

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Project description:deBack2012 - Lineage Specification in Pancreas Development This model of two neighbouring pancreas precursor cells, describes the exocrine versus endocrine lineage specification process. To account for the tissue scale patterns, this couplet model has been extended to hundreds of coupled cells. This model is described in the article: On the role of lateral stabilization during early patterning in the pancreas de Back W., Zhou JX, Brusch L J. R. Soc. Interface 6 February 2013 vol. 10 no. 79 20120766 Abstract: The cell fate decision of multi-potent pancreatic progenitor cells between the exocrine and endocrine lineages is regulated by Notch signalling, mediated by cell–cell interactions. However, canonical models of Notch-mediated lateral inhibition cannot explain the scattered spatial distribution of endocrine cells and the cell-type ratio in the developing pancreas. Based on evidence from acinar-to-islet cell transdifferentiation in vitro, we propose that lateral stabilization, i.e. positive feedback between adjacent progenitor cells, acts in parallel with lateral inhibition to regulate pattern formation in the pancreas. A simple mathematical model of transcriptional regulation and cell–cell interaction reveals the existence of multi-stability of spatial patterns whose simultaneous occurrence causes scattering of endocrine cells in the presence of noise. The scattering pattern allows for control of the endocrine-to-exocrine cell-type ratio by modulation of lateral stabilization strength. These theoretical results suggest a previously unrecognized role for lateral stabilization in lineage specification, spatial patterning and cell-type ratio control in organ development. This model is hosted on BioModels Database and identified by: MODEL1211010000 . To cite BioModels Database, please use: BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models . To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication for more information.

Project description:Chickarmane2008 - Stem cell lineage determination In this work, a dynamical model of lineage determination based upon a minimal circuit, as discussed in PMID: 17215298 , which contains the Oct4/Sox2/Nanog core as well its interaction with a few other key genes is discussed. This model is described in the article: A computational model for understanding stem cell, trophectoderm and endoderm lineage determination. Chickarmane V, Peterson C PloS one. 2008, 3(10):e3478 Abstract: BACKGROUND: Recent studies have associated the transcription factors, Oct4, Sox2 and Nanog as parts of a self-regulating network which is responsible for maintaining embryonic stem cell properties: self renewal and pluripotency. In addition, mutual antagonism between two of these and other master regulators have been shown to regulate lineage determination. In particular, an excess of Cdx2 over Oct4 determines the trophectoderm lineage whereas an excess of Gata-6 over Nanog determines differentiation into the endoderm lineage. Also, under/over-expression studies of the master regulator Oct4 have revealed that some self-renewal/pluripotency as well as differentiation genes are expressed in a biphasic manner with respect to the concentration of Oct4. METHODOLOGY/ PRINCIPAL FINDINGS: We construct a dynamical model of a minimalistic network, extracted from ChIP-on-chip and microarray data as well as literature studies. The model is based upon differential equations and makes two plausible assumptions; activation of Gata-6 by Oct4 and repression of Nanog by an Oct4-Gata-6 heterodimer. With these assumptions, the results of simulations successfully describe the biphasic behavior as well as lineage commitment. The model also predicts that reprogramming the network from a differentiated state, in particular the endoderm state, into a stem cell state, is best achieved by over-expressing Nanog, rather than by suppression of differentiation genes such as Gata-6. CONCLUSIONS: The computational model provides a mechanistic understanding of how different lineages arise from the dynamics of the underlying regulatory network. It provides a framework to explore strategies of reprogramming a cell from a differentiated state to a stem cell state through directed perturbations. Such an approach is highly relevant to regenerative medicine since it allows for a rapid search over the host of possibilities for reprogramming to a stem cell state. This model is hosted on BioModels Database and identified by: MODEL8390025091 . To cite BioModels Database, please use: BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models . To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication for more information.

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Dataset Information

Molecular architecture of lineage specification and tissue organization in early mouse embryo

Publications

Molecular architecture of lineage allocation and tissue organization in early mouse embryo.

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