Inferring rules of lineage commitment in haematopoiesis
(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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/2379357
- author
- Pina, Cristina ; Fugazza, Cristina ; Tipping, Alex J. ; Brown, John ; Soneji, Shamit ; Teles, José LU ; Peterson, Carsten LU and Enver, Tariq
- organization
- publishing date
- 2012
- 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
- pmid:22344032
- 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
- 2016-04-01 14:10:41
- date last changed
- 2022-12-11 22:22:34
@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}},
doi = {{10.1038/ncb2442}},
volume = {{14}},
year = {{2012}},
}