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

Golkaram, Mahdi; Jang, Jiwon; Hellander, Stefan; Kosik, Kenneth S.; Petzold, Linda R.

doi:10.1038/s41598-017-13731-3

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

Journal Article · 17 October 2017 · Scientific Reports

DOI: https://doi.org/10.1038/s41598-017-13731-3 · OSTI ID:1500036

Golkaram, Mahdi ^[1]; Jang, Jiwon ^[1]; Hellander, Stefan ^[2]; Kosik, Kenneth S. ^[1]; Petzold, Linda R. ^[1]

Univ. of California, Santa Barbara, CA (United States)
Univ. of California, Santa Barbara, CA (United States); Uppsala Univ. (Sweden)

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.

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Research Organization:: Univ. of California, Santa Barbara, CA (United States)

Sponsoring Organization:: USDOE

Grant/Contract Number:: SC0008975

OSTI ID:: 1500036

Journal Information:: Scientific Reports, Vol. 7, Issue 1; ISSN 2045-2322

Publisher:: Nature Publishing GroupCopyright Statement

Country of Publication:: United States

Language:: English

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