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Title: The Role of Chromatin Density in Cell Population Heterogeneity during Stem Cell Differentiation

Abstract

We incorporate three-dimensional (3D) conformation of chromosome (Hi-C) and single-cell RNA sequencing data together with discrete stochastic simulation, to explore the role of chromatin reorganization in determining gene expression heterogeneity during development. While previous research has emphasized the importance of chromatin architecture on activation and suppression of certain regulatory genes and gene networks, our study demonstrates how chromatin remodeling can dictate gene expression distribution by folding into distinct topological domains. We hypothesize that the local DNA density during differentiation accentuate transcriptional bursting due to the crowding effect of chromatin. This phenomenon yields a heterogeneous cell population, thereby increasing the potential of differentiation of the stem cells.

Authors:
 [1];  [1];  [2];  [1];  [1]
+ Show Author Affiliations
  1. Univ. of California, Santa Barbara, CA (United States)
  2. Univ. of California, Santa Barbara, CA (United States); Uppsala Univ. (Sweden)
Publication Date:
Research Org.:
Univ. of California, Santa Barbara, CA (United States)
Sponsoring Org.:
USDOE
OSTI Identifier:
1500036
Grant/Contract Number:  
SC0008975
Resource Type:
Accepted Manuscript
Journal Name:
Scientific Reports
Additional Journal Information:
Journal Volume: 7; Journal Issue: 1; Journal ID: ISSN 2045-2322
Publisher:
Nature Publishing Group
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES

Citation Formats

Golkaram, Mahdi, Jang, Jiwon, Hellander, Stefan, Kosik, Kenneth S., and Petzold, Linda R. The Role of Chromatin Density in Cell Population Heterogeneity during Stem Cell Differentiation. United States: N. p., 2017. Web. doi:10.1038/s41598-017-13731-3.
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Golkaram, Mahdi, Jang, Jiwon, Hellander, Stefan, Kosik, Kenneth S., & Petzold, Linda R. The Role of Chromatin Density in Cell Population Heterogeneity during Stem Cell Differentiation. United States. https://doi.org/10.1038/s41598-017-13731-3
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Golkaram, Mahdi, Jang, Jiwon, Hellander, Stefan, Kosik, Kenneth S., and Petzold, Linda R. Tue . "The Role of Chromatin Density in Cell Population Heterogeneity during Stem Cell Differentiation". United States. https://doi.org/10.1038/s41598-017-13731-3. https://www.osti.gov/servlets/purl/1500036.
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@article{osti_1500036,
title = {The Role of Chromatin Density in Cell Population Heterogeneity during Stem Cell Differentiation},
author = {Golkaram, Mahdi and Jang, Jiwon and Hellander, Stefan and Kosik, Kenneth S. and Petzold, Linda R.},
abstractNote = {We incorporate three-dimensional (3D) conformation of chromosome (Hi-C) and single-cell RNA sequencing data together with discrete stochastic simulation, to explore the role of chromatin reorganization in determining gene expression heterogeneity during development. While previous research has emphasized the importance of chromatin architecture on activation and suppression of certain regulatory genes and gene networks, our study demonstrates how chromatin remodeling can dictate gene expression distribution by folding into distinct topological domains. We hypothesize that the local DNA density during differentiation accentuate transcriptional bursting due to the crowding effect of chromatin. This phenomenon yields a heterogeneous cell population, thereby increasing the potential of differentiation of the stem cells.},
doi = {10.1038/s41598-017-13731-3},
journal = {Scientific Reports},
number = 1,
volume = 7,
place = {United States},
year = {2017},
month = {10}
}
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Journal Article:
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Publisher's Version of Record
https://doi.org/10.1038/s41598-017-13731-3
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Cited by: 3 works
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Figures / Tables:

Figure 1 Figure 1: Macromolecular crowding model of gene expression. (a) MCMC simulations show a lack of interchromosomal entanglement. Schematic illustration of the density sphere around an arbitrary gene locus is provided on the right. (b) cumulative radial distribution function of DNA bps around the SOX2 gene locus demonstrates the local densitymore » variation between hESC and NPC. (c) density increases significantly during hESC differentiation (***p-value < 0.001). (d) binary model of gene expression for gene activating and repressing transcription factors. (e and f) bifurcation diagrams of gene expression for transcriptionally activated (e) and repressed (h) genes. (f) pulse frequency analysis of transcriptional bursting. (g) bimodality inspection during chromatin condensation by Hartigan’s Dip test. (i) population heterogeneity induced by transcriptional bursting and chromatin condensation. (j) steady state gene expression distribution variation during stem cell differentiation aroused from chromatin condensation.« less
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