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Inferring rules of lineage commitment in haematopoiesis

Pina, Cristina; Fugazza, Cristina; Tipping, Alex J.; Brown, John; Soneji, Shamit; Teles, José LU ; Peterson, Carsten LU and Enver, Tariq (2012) In Nature Cell Biology 14(3). p.287-287
Abstract
How the molecular programs of differentiated cells develop as cells transit from multipotency through lineage commitment remains unexplored. This reflects the inability to access cells undergoing commitment or located in the immediate vicinity of commitment boundaries. It remains unclear whether commitment constitutes a gradual process, or else represents a discrete transition. Analyses of in vitro self-renewing multipotent systems have revealed cellular heterogeneity with individual cells transiently exhibiting distinct biases for lineage commitment(1-6). Such systems can be used to molecularly interrogate early stages of lineage affiliation and infer rules of lineage commitment. In haematopoiesis, population-based studies have indicated... (More)
How the molecular programs of differentiated cells develop as cells transit from multipotency through lineage commitment remains unexplored. This reflects the inability to access cells undergoing commitment or located in the immediate vicinity of commitment boundaries. It remains unclear whether commitment constitutes a gradual process, or else represents a discrete transition. Analyses of in vitro self-renewing multipotent systems have revealed cellular heterogeneity with individual cells transiently exhibiting distinct biases for lineage commitment(1-6). Such systems can be used to molecularly interrogate early stages of lineage affiliation and infer rules of lineage commitment. In haematopoiesis, population-based studies have indicated that lineage choice is governed by global transcriptional noise, with self-renewing multipotent cells reversibly activating transcriptome-wide lineage-affiliated programs(7). We examine this hypothesis through functional and molecular analysis of individual blood cells captured from self-renewal cultures, during cytokine-driven differentiation and from primary stem and progenitor bone marrow compartments. We show dissociation between self-renewal potential and transcriptome-wide activation of lineage programs, and instead suggest that multipotent cells experience independent activation of individual regulators resulting in a low probability of transition to the committed state. (Less)
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type
Contribution to journal
publication status
published
subject
in
Nature Cell Biology
volume
14
issue
3
pages
287 - 287
publisher
Nature Publishing Group
external identifiers
  • wos:000300930400011
  • scopus:84862778068
ISSN
1465-7392
DOI
10.1038/ncb2442
language
English
LU publication?
yes
id
ccadc230-1534-4a9c-931c-09413780a933 (old id 2379357)
date added to LUP
2012-03-30 14:44:33
date last changed
2017-11-12 03:43:37
@article{ccadc230-1534-4a9c-931c-09413780a933,
  abstract     = {How the molecular programs of differentiated cells develop as cells transit from multipotency through lineage commitment remains unexplored. This reflects the inability to access cells undergoing commitment or located in the immediate vicinity of commitment boundaries. It remains unclear whether commitment constitutes a gradual process, or else represents a discrete transition. Analyses of in vitro self-renewing multipotent systems have revealed cellular heterogeneity with individual cells transiently exhibiting distinct biases for lineage commitment(1-6). Such systems can be used to molecularly interrogate early stages of lineage affiliation and infer rules of lineage commitment. In haematopoiesis, population-based studies have indicated that lineage choice is governed by global transcriptional noise, with self-renewing multipotent cells reversibly activating transcriptome-wide lineage-affiliated programs(7). We examine this hypothesis through functional and molecular analysis of individual blood cells captured from self-renewal cultures, during cytokine-driven differentiation and from primary stem and progenitor bone marrow compartments. We show dissociation between self-renewal potential and transcriptome-wide activation of lineage programs, and instead suggest that multipotent cells experience independent activation of individual regulators resulting in a low probability of transition to the committed state.},
  author       = {Pina, Cristina and Fugazza, Cristina and Tipping, Alex J. and Brown, John and Soneji, Shamit and Teles, José and Peterson, Carsten and Enver, Tariq},
  issn         = {1465-7392},
  language     = {eng},
  number       = {3},
  pages        = {287--287},
  publisher    = {Nature Publishing Group},
  series       = {Nature Cell Biology},
  title        = {Inferring rules of lineage commitment in haematopoiesis},
  url          = {http://dx.doi.org/10.1038/ncb2442},
  volume       = {14},
  year         = {2012},
}