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Cell dynamics and gene expression control in tissue homeostasis and development.

Rué P, Martinez Arias A - Mol. Syst. Biol. (2015)

Bottom Line: While some of the basic principles underlying these processes developing and maintaining these organs are known, much remains to be learnt from how cells encode the necessary information and use it to attain those complex but reproducible arrangements.We propose a framework, involving the existence of a transition state in which cells are more susceptible to signals that can affect their gene expression state and influence their cell fate decisions.This framework, which also applies to systems much more amenable to quantitative analysis like differentiating embryonic stem cells, links gene expression programmes with cell population dynamics.

View Article: PubMed Central - PubMed

Affiliation: Department of Genetics, University of Cambridge, Cambridge, UK.

No MeSH data available.


Related in: MedlinePlus

Molecular mechanisms of self-renewal and differentiation: the transition state(A) The concept of the transition state (TS) between an origin (o) and a destination (d) state. During a fate change, a cell goes through a TS (for details see text), which implies the existence of kinetic constants governing the transitions between different states. (B) The TS can be observed in mouse ESCs. In this case, this is shown within the framework of Nanog expression, which is heterogeneously expressed with three distinguishable populations: o, representing ground state pluripotency; d, where it is possible to find cells committed to differentiation and TS where cells make a choice. (C) The coexistence of committed and uncommitted cells in the Nanog:GFP d population can be revealed by looking at a second pluripotency marker, Pecam or SSEA1 in this case (Canham et al, 2010; Lim, 2011). (D) A similar scenario has been recently observed in blood stem cells: cells with high levels of Sca1 can self-renew and are in a state analogous to the ‘o’ state. Sca1 low cells further subdivide into two populations, which can be identified by CD34. Sca1−/CD34+ have repopulation capacity and can revert to Sca1+ while the Sca1−/CD34− population consists of erythroid commited cells with no self-renewal capacity.
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fig02: Molecular mechanisms of self-renewal and differentiation: the transition state(A) The concept of the transition state (TS) between an origin (o) and a destination (d) state. During a fate change, a cell goes through a TS (for details see text), which implies the existence of kinetic constants governing the transitions between different states. (B) The TS can be observed in mouse ESCs. In this case, this is shown within the framework of Nanog expression, which is heterogeneously expressed with three distinguishable populations: o, representing ground state pluripotency; d, where it is possible to find cells committed to differentiation and TS where cells make a choice. (C) The coexistence of committed and uncommitted cells in the Nanog:GFP d population can be revealed by looking at a second pluripotency marker, Pecam or SSEA1 in this case (Canham et al, 2010; Lim, 2011). (D) A similar scenario has been recently observed in blood stem cells: cells with high levels of Sca1 can self-renew and are in a state analogous to the ‘o’ state. Sca1 low cells further subdivide into two populations, which can be identified by CD34. Sca1−/CD34+ have repopulation capacity and can revert to Sca1+ while the Sca1−/CD34− population consists of erythroid commited cells with no self-renewal capacity.

Mentions: One interpretation of this observation is provided by the notion of multilineage priming (Hu et al, 1997). According to this notion, a characteristic of a stem cell population is the expression of markers of multiple lineages at low levels, which creates a landscape of differentiation potential (Moignard & Göttgens, 2014). A related view is contained in the ‘transition state’ (Fig2A), a concept derived from the observation that when cells change state during development, the decision is taken by individual cells from a ‘transition state’ (TS), in which a cell transiently exhibits a mixed identity between the states we could call origin (o) and destination (d) (Fig2A; Martinez Arias & Hayward, 2006; Muñoz Descalzo & Martinez Arias, 2012). At the TS, a cell has a probability of returning to o or moving to d, and its mixed identity is reflected in simultaneous, though variable, expression of genes from both states in the same cell. Once a cell moves from the TS towards the d state, the progression becomes irreversible. In a population undergoing a state transition between two states (o and d), this results in a mixture of cells in one of three states: o,TS and d. Such heterogeneous patterns of gene expression are often observed in developmental systems. If one associates a self-renewal rate to cells in o and TS and balances the ratios of transition of this self-renewal with differentiation, the result is something that formally resembles a stem cell population, which thus could be construed as a self-replicating transition state (Muñoz-Descalzo et al, 2012). The TS is a crucial step during the cell fate decision process, and this contrasts with the notion of lineage priming that merely describes a population in a steady state.


Cell dynamics and gene expression control in tissue homeostasis and development.

Rué P, Martinez Arias A - Mol. Syst. Biol. (2015)

Molecular mechanisms of self-renewal and differentiation: the transition state(A) The concept of the transition state (TS) between an origin (o) and a destination (d) state. During a fate change, a cell goes through a TS (for details see text), which implies the existence of kinetic constants governing the transitions between different states. (B) The TS can be observed in mouse ESCs. In this case, this is shown within the framework of Nanog expression, which is heterogeneously expressed with three distinguishable populations: o, representing ground state pluripotency; d, where it is possible to find cells committed to differentiation and TS where cells make a choice. (C) The coexistence of committed and uncommitted cells in the Nanog:GFP d population can be revealed by looking at a second pluripotency marker, Pecam or SSEA1 in this case (Canham et al, 2010; Lim, 2011). (D) A similar scenario has been recently observed in blood stem cells: cells with high levels of Sca1 can self-renew and are in a state analogous to the ‘o’ state. Sca1 low cells further subdivide into two populations, which can be identified by CD34. Sca1−/CD34+ have repopulation capacity and can revert to Sca1+ while the Sca1−/CD34− population consists of erythroid commited cells with no self-renewal capacity.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4358661&req=5

fig02: Molecular mechanisms of self-renewal and differentiation: the transition state(A) The concept of the transition state (TS) between an origin (o) and a destination (d) state. During a fate change, a cell goes through a TS (for details see text), which implies the existence of kinetic constants governing the transitions between different states. (B) The TS can be observed in mouse ESCs. In this case, this is shown within the framework of Nanog expression, which is heterogeneously expressed with three distinguishable populations: o, representing ground state pluripotency; d, where it is possible to find cells committed to differentiation and TS where cells make a choice. (C) The coexistence of committed and uncommitted cells in the Nanog:GFP d population can be revealed by looking at a second pluripotency marker, Pecam or SSEA1 in this case (Canham et al, 2010; Lim, 2011). (D) A similar scenario has been recently observed in blood stem cells: cells with high levels of Sca1 can self-renew and are in a state analogous to the ‘o’ state. Sca1 low cells further subdivide into two populations, which can be identified by CD34. Sca1−/CD34+ have repopulation capacity and can revert to Sca1+ while the Sca1−/CD34− population consists of erythroid commited cells with no self-renewal capacity.
Mentions: One interpretation of this observation is provided by the notion of multilineage priming (Hu et al, 1997). According to this notion, a characteristic of a stem cell population is the expression of markers of multiple lineages at low levels, which creates a landscape of differentiation potential (Moignard & Göttgens, 2014). A related view is contained in the ‘transition state’ (Fig2A), a concept derived from the observation that when cells change state during development, the decision is taken by individual cells from a ‘transition state’ (TS), in which a cell transiently exhibits a mixed identity between the states we could call origin (o) and destination (d) (Fig2A; Martinez Arias & Hayward, 2006; Muñoz Descalzo & Martinez Arias, 2012). At the TS, a cell has a probability of returning to o or moving to d, and its mixed identity is reflected in simultaneous, though variable, expression of genes from both states in the same cell. Once a cell moves from the TS towards the d state, the progression becomes irreversible. In a population undergoing a state transition between two states (o and d), this results in a mixture of cells in one of three states: o,TS and d. Such heterogeneous patterns of gene expression are often observed in developmental systems. If one associates a self-renewal rate to cells in o and TS and balances the ratios of transition of this self-renewal with differentiation, the result is something that formally resembles a stem cell population, which thus could be construed as a self-replicating transition state (Muñoz-Descalzo et al, 2012). The TS is a crucial step during the cell fate decision process, and this contrasts with the notion of lineage priming that merely describes a population in a steady state.

Bottom Line: While some of the basic principles underlying these processes developing and maintaining these organs are known, much remains to be learnt from how cells encode the necessary information and use it to attain those complex but reproducible arrangements.We propose a framework, involving the existence of a transition state in which cells are more susceptible to signals that can affect their gene expression state and influence their cell fate decisions.This framework, which also applies to systems much more amenable to quantitative analysis like differentiating embryonic stem cells, links gene expression programmes with cell population dynamics.

View Article: PubMed Central - PubMed

Affiliation: Department of Genetics, University of Cambridge, Cambridge, UK.

No MeSH data available.


Related in: MedlinePlus