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

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

doi:10.1038/s41598-017-13731-3

Cited by 19 publications

(21 citation statements)

References 63 publications

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“…Progressive restriction of cell fates and cell differentiation occur with global chromatin remodeling that results in progressively compacted, repressed chromatin that corresponds with activation of lineage-specific genes and repression of lineage-inappropriate genes [125][126][127]. Such progressive restriction of genome transcription is consistent with the recent findings, discussed earlier, that the early-generated neuronal cells express a wider variety of transcripts than the later-generated glial cells [31,32].…”

Section: Why Should Glial Cell Size Be Constrained?supporting

confidence: 88%

You Do Not Mess with the Glia

Herculano‐Houzel

Santos

2018

Neuroglia

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Vertebrate neurons are enormously variable in morphology and distribution. While different glial cell types do exist, they are much less diverse than neurons. Over the last decade, we have conducted quantitative studies of the absolute numbers, densities, and proportions at which non-neuronal cells occur in relation to neurons. These studies have advanced the notion that glial cells are much more constrained than neurons in how much they can vary in both development and evolution. Recent evidence from studies on gene expression profiles that characterize glial cells-in the context of progressive epigenetic changes in chromatin during morphogenesis-supports the notion of constrained variation of glial cells in development and evolution, and points to the possibility that this constraint is related to the late differentiation of the various glial cell types. Whether restricted variation is a biological given (a simple consequence of late glial cell differentiation) or a physiological constraint (because, well, you do not mess with the glia without consequences that compromise brain function to the point of rendering those changes unviable), we predict that the restricted variation in size and distribution of glial cells has important consequences for neural tissue function that is aligned with their many fundamental roles being uncovered.

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Section: Why Should Glial Cell Size Be Constrained?supporting

confidence: 88%

You Do Not Mess with the Glia

Herculano‐Houzel

Santos

2018

Neuroglia

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“…Given the transcription-dependent incorporation mode of H3.3 (Ahmad & Henikoff, 2002b, Tagami et al, 2004, it is possible that this biased H3.3 inheritance contributes to or correlates with higher transcriptional activities in GSCs compared to CBs. These results are consistent with previous reports that stem cells maintain an overall more open chromatin state and their differentiated cells begin to "lock down" their chromatin towards a more restricted cell fate (Gaspar-Maia, Alajem et al, 2011, Golkaram, Jang et al, 2017, Turner, 2008, Yu, Wu et al, 2017).…”

Section: Dividing Female Gscs and Cbs Show Globally Symmetric But Locsupporting

confidence: 92%

Characterization of histone inheritance patterns in theDrosophilafemale germline

Kahney

Sohn

Viets-Layng

et al. 2020

Preprint

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Stem cells have the unique ability to undergo asymmetric division which produces two daughter cells that are genetically identical, but commit to different cell fates. The loss of this balanced asymmetric outcome can lead to many diseases, including cancer and tissue dystrophy. Understanding this tightly regulated process is crucial in developing methods to treat these abnormalities. Here, we report that produced from a Drosophila female germline stem cell asymmetric division, the two daughter cells differentially inherit histones at key genes related to either maintaining the stem cell state or promoting differentiation, but not at constitutively active or silenced genes. We combined histone labeling with DNA Oligopaints to distinguish old versus new histone distribution and visualize their inheritance patterns at single-gene resolution in asymmetrically dividing cells in vivo. This strategy can be widely applied to other biological contexts involving cell fate establishment during development or tissue homeostasis in multicellular organisms.

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“…How this fine-scale topology connects with chromatin function, notably gene expression, requires a biophysical appraisal of chromatin organization. Emerging models linking molecular-to-spatial (macromolecular) levels of chromatin dynamics are very attractive to explain the emergence of transcriptional dynamics during cellular differentiation [70]. Notably, local nucleosomal arrays appear to connect with molecular crowding, a dynamic property directly influencing the access and residence of the transcription machinery to chromosomal regions [57, 70].…”

Section: Discussionmentioning

confidence: 99%

Linker histones are fine-scale chromatin architects modulating developmental decisions in Arabidopsis

et al. 2019

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Background Chromatin provides a tunable platform for gene expression control. Besides the well-studied core nucleosome, H1 linker histones are abundant chromatin components with intrinsic potential to influence chromatin function. Well studied in animals, little is known about the evolution of H1 function in other eukaryotic lineages for instance plants. Notably, in the model plant Arabidopsis , while H1 is known to influence heterochromatin and DNA methylation, its contribution to transcription, molecular, and cytological chromatin organization remains elusive. Results We provide a multi-scale functional study of Arabidopsis linker histones. We show that H1-deficient plants are viable yet show phenotypes in seed dormancy, flowering time, lateral root, and stomata formation—complemented by either or both of the major variants. H1 depletion also impairs pluripotent callus formation. Fine-scale chromatin analyses combined with transcriptome and nucleosome profiling reveal distinct roles of H1 on hetero- and euchromatin: H1 is necessary to form heterochromatic domains yet dispensable for silencing of most transposable elements; H1 depletion affects nucleosome density distribution and mobility in euchromatin, spatial arrangement of nanodomains, histone acetylation, and methylation. These drastic changes affect moderately the transcription but reveal a subset of H1-sensitive genes. Conclusions H1 variants have a profound impact on the molecular and spatial (nuclear) chromatin organization in Arabidopsis with distinct roles in euchromatin and heterochromatin and a dual causality on gene expression. Phenotypical analyses further suggest the novel possibility that H1-mediated chromatin organization may contribute to the epigenetic control of developmental and cellular transitions. Electronic supplementary material The online version of this article (10.1186/s13059-019-1767-3) contains supplementary material, which is available to authorized users.

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

Cited by 19 publications

References 63 publications

You Do Not Mess with the Glia

You Do Not Mess with the Glia

Characterization of histone inheritance patterns in theDrosophilafemale germline

Linker histones are fine-scale chromatin architects modulating developmental decisions in Arabidopsis

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