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Haematopoietic stem cells : Entropic landscapes of differentiation

Wiesner, K. ; Teles, J. LU ; Hartnor, M. and Peterson, C. LU (2018) In Interface Focus 8(6).
Abstract

The metaphor of a potential epigenetic differentiation landscape broadly suggests that during differentiation a stem cell approaches a stable equilibrium state from a higher free energy towards a stable equilibrium state which represents the final cell type. It has been conjectured that there is an analogy to the concept of entropy in statistical mechanics. In this context, in the undifferentiated state, the entropy would be large since fewer constraints exist on the gene expression programmes of the cell. As differentiation progresses, gene expression programmes become more and more constrained and thus the entropy would be expected to decrease. In order to assess these predictions, we compute the Shannon entropy for time-resolved... (More)

The metaphor of a potential epigenetic differentiation landscape broadly suggests that during differentiation a stem cell approaches a stable equilibrium state from a higher free energy towards a stable equilibrium state which represents the final cell type. It has been conjectured that there is an analogy to the concept of entropy in statistical mechanics. In this context, in the undifferentiated state, the entropy would be large since fewer constraints exist on the gene expression programmes of the cell. As differentiation progresses, gene expression programmes become more and more constrained and thus the entropy would be expected to decrease. In order to assess these predictions, we compute the Shannon entropy for time-resolved single-cell gene expression data in two different experimental set-ups of haematopoietic differentiation. We find that the behaviour of this entropy measure is in contrast to these predictions. In particular, we find that the Shannon entropy is not a decreasing function of developmental pseudo-time but instead it increases towards the time point of commitment before decreasing again. This behaviour is consistent with an increase in gene expression disorder observed in populations sampled at the time point of commitment. Single cells in these populations exhibit different combinations of regulator activity that suggest the presence of multiple configurations of a potential differentiation network as a result of multiple entry points into the committed state.

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author
; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Entropy, Shannon information theory, Stem cell differentiation
in
Interface Focus
volume
8
issue
6
article number
20180040
publisher
Royal Society Publishing
external identifiers
  • scopus:85056555608
  • pmid:30443337
ISSN
2042-8898
DOI
10.1098/rsfs.2018.0040
language
English
LU publication?
yes
id
6e56e4ea-228f-4ee5-974e-fda863fad336
date added to LUP
2018-11-26 13:03:41
date last changed
2021-09-08 03:39:37
@article{6e56e4ea-228f-4ee5-974e-fda863fad336,
  abstract     = {<p>The metaphor of a potential epigenetic differentiation landscape broadly suggests that during differentiation a stem cell approaches a stable equilibrium state from a higher free energy towards a stable equilibrium state which represents the final cell type. It has been conjectured that there is an analogy to the concept of entropy in statistical mechanics. In this context, in the undifferentiated state, the entropy would be large since fewer constraints exist on the gene expression programmes of the cell. As differentiation progresses, gene expression programmes become more and more constrained and thus the entropy would be expected to decrease. In order to assess these predictions, we compute the Shannon entropy for time-resolved single-cell gene expression data in two different experimental set-ups of haematopoietic differentiation. We find that the behaviour of this entropy measure is in contrast to these predictions. In particular, we find that the Shannon entropy is not a decreasing function of developmental pseudo-time but instead it increases towards the time point of commitment before decreasing again. This behaviour is consistent with an increase in gene expression disorder observed in populations sampled at the time point of commitment. Single cells in these populations exhibit different combinations of regulator activity that suggest the presence of multiple configurations of a potential differentiation network as a result of multiple entry points into the committed state.</p>},
  author       = {Wiesner, K. and Teles, J. and Hartnor, M. and Peterson, C.},
  issn         = {2042-8898},
  language     = {eng},
  month        = {12},
  number       = {6},
  publisher    = {Royal Society Publishing},
  series       = {Interface Focus},
  title        = {Haematopoietic stem cells : Entropic landscapes of differentiation},
  url          = {http://dx.doi.org/10.1098/rsfs.2018.0040},
  doi          = {10.1098/rsfs.2018.0040},
  volume       = {8},
  year         = {2018},
}