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:
-
- Univ. of California, Santa Barbara, CA (United States)
- 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.
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
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.
@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 = {Tue Oct 17 00:00:00 EDT 2017},
month = {Tue Oct 17 00:00:00 EDT 2017}
}
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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 »
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Linker histones are fine-scale chromatin architects modulating developmental decisions in Arabidopsis
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