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Stochastic priming and spatial cues orchestrate heterogeneous clonal contribution to mouse pancreas organogenesis.

ABSTRACT: Spatiotemporal balancing of cellular proliferation and differentiation is crucial for postnatal tissue homoeostasis and organogenesis. During embryonic development, pancreatic progenitors simultaneously proliferate and differentiate into the endocrine, ductal and acinar lineages. Using in vivo clonal analysis in the founder population of the pancreas here we reveal highly heterogeneous contribution of single progenitors to organ formation. While some progenitors are bona fide multipotent and contribute progeny to all major pancreatic cell lineages, we also identify numerous unipotent endocrine and ducto-endocrine bipotent clones. Single-cell transcriptional profiling at E9.5 reveals that endocrine-committed cells are molecularly distinct, whereas multipotent and bipotent progenitors do not exhibit different expression profiles. Clone size and composition support a probabilistic model of cell fate allocation and in silico simulations predict a transient wave of acinar differentiation around E11.5, while endocrine differentiation is proportionally decreased. Increased proliferative capacity of outer progenitors is further proposed to impact clonal expansion.

SUBMITTER: Larsen HL

PROVIDER: S-EPMC5605525 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature

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Stochastic priming and spatial cues orchestrate heterogeneous clonal contribution to mouse pancreas organogenesis.

Larsen Hjalte List HL Martín-Coll Laura L Nielsen Alexander Valentin AV Wright Christopher V E CVE Trusina Ala A Kim Yung Hae YH Grapin-Botton Anne A

Nature communications 20170919 1

Spatiotemporal balancing of cellular proliferation and differentiation is crucial for postnatal tissue homoeostasis and organogenesis. During embryonic development, pancreatic progenitors simultaneously proliferate and differentiate into the endocrine, ductal and acinar lineages. Using in vivo clonal analysis in the founder population of the pancreas here we reveal highly heterogeneous contribution of single progenitors to organ formation. While some progenitors are bona fide multipotent and con ...[more]

PMID: 28928395

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Project description:BackgroundInfectious diseases such as SARS and H1N1 can significantly impact people's lives and cause severe social and economic damages. Recent outbreaks have stressed the urgency of effective research on the dynamics of infectious disease spread. However, it is difficult to predict when and where outbreaks may emerge and how infectious diseases spread because many factors affect their transmission, and some of them may be unknown.MethodsOne feasible means to promptly detect an outbreak and track the progress of disease spread is to implement surveillance systems in regional or national health and medical centres. The accumulated surveillance data, including temporal, spatial, clinical, and demographic information can provide valuable information that can be exploited to better understand and model the dynamics of infectious disease spread. The aim of this work is to develop and empirically evaluate a stochastic model that allows the investigation of transmission patterns of infectious diseases in heterogeneous populations.ResultsWe test the proposed model on simulation data and apply it to the surveillance data from the 2009 H1N1 pandemic in Hong Kong. In the simulation experiment, our model achieves high accuracy in parameter estimation (less than 10.0 % mean absolute percentage error). In terms of the forward prediction of case incidence, the mean absolute percentage errors are 17.3 % for the simulation experiment and 20.0 % for the experiment on the real surveillance data.ConclusionWe propose a stochastic model to study the dynamics of infectious disease spread in heterogeneous populations from temporal-spatial surveillance data. The proposed model is evaluated using both simulated data and the real data from the 2009 H1N1 epidemic in Hong Kong and achieves acceptable prediction accuracy. We believe that our model can provide valuable insights for public health authorities to predict the effect of disease spread and analyse its underlying factors and to guide new control efforts.

Dataset Information

Stochastic priming and spatial cues orchestrate heterogeneous clonal contribution to mouse pancreas organogenesis.

Publications

Stochastic priming and spatial cues orchestrate heterogeneous clonal contribution to mouse pancreas organogenesis.

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