Title :

Network Features and Dynamical Landscape of Naive and Primed Pluripotency

Author(s) :

Pfeuty, Benjamin [Auteur]
Laboratoire de Physique des Lasers, Atomes et Molécules - UMR 8523 [PhLAM]
Kress, Clémence [Auteur]
Unité de recherche génomique et physiologie de la lactation [GPL]
Pain, Bertrand [Auteur]
Institut cellule souche et cerveau [U846 Inserm - UCBL1]

Journal title :

Biophysical Journal

Pages :

237-248

Publisher :

Biophysical Society

Publication date :

2018-01

ISSN :

0006-3495

Keyword(s) :

transcriptional regulation
oct4 expression

English keyword(s) :

embryonic stem-cells
ground-state pluripotency
gene regulatory network
self-renewal
lineage-commitment
mouse epiblast
endoderm differentiation
nanog expression

HAL domain(s) :

Sciences du Vivant [q-bio]

English abstract : [en]

Although the broad and unique differentiation potential of pluripotent stem cells relies on a complex transcriptional network centered around Oct4, Sox2, and Nanog, two well-distinct pluripotent states, called "naive'' and ...
Show more >Although the broad and unique differentiation potential of pluripotent stem cells relies on a complex transcriptional network centered around Oct4, Sox2, and Nanog, two well-distinct pluripotent states, called "naive'' and "primed'', have been described in vitro and markedly differ in their developmental potential, their expression profiles, their signaling requirements, and their reciprocal conversion. Aiming to determine the key features that segregate and coordinate these two states, data-driven optimization of network models is performed to identify relevant parameter regimes and reduce network complexity to its core structure. Decision dynamics of optimized networks is characterized by signal-dependent multistability and strongly asymmetric transitions among naive, primed, and nonpluripotent states. Further model perturbation and reduction approaches reveal that such a dynamical landscape of pluripotency involves a functional partitioning of the regulatory network. Specifically, two overlapping positive feedback modules, Klf4/Esrrb/Nanog and Oct4/Nanog, stabilize the naive or the primed state, respectively. In turn, their incoherent feedforward and negative feedback coupling mediated by the Erk/Gsk3 module is critical for robust segregation and sequential progression between naive and primed states before irreversible exit from pluripotency.Show less >

Language :

Anglais

Peer reviewed article :

Oui

Audience :

Internationale

Popular science :

Non

Collections :

• Laboratoire de Physique des Lasers, Atomes et Molécules (PhLAM) - UMR 8523

Source :

Harvested from HAL