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Cell fate decision circuits must be variable enough for genetically identical cells to adopt a multitude of fates, yet ensure that these states are distinct, stably maintained, and coordinated with neighboring cells. A long-standing view is that this is achieved by regulatory networks involving self-stabilizing feedback loops that convert small differences into long-lived cell types. We combined regulatory mutants and in vivo reconstitution with theory for stochastic processes to show that the marquee features of a cell fate switch in -discrete states, multigenerational inheritance, and timing of commitments-can instead be explained by simple stochastic competition between two constitutively produced proteins that form an inactive complex. Such antagonistic interactions are commonplace in cells and could provide powerful mechanisms for cell fate determination more broadly.
This article was published in the following journal.
Name: Science (New York, N.Y.)
Stem cells are continuously challenged with the decision to either self-renew or adopt a new fate. Self-renewal is regulated by a system of cellular memory, which must be bypassed for differentiation....
Gliosis defined as reactive changes of resident glia is the primary response of the central nervous system (CNS) to trauma. The proliferation and fate controls of injury-reactivated glia are essential...
Phenotypic heterogeneity in cancer cells is widely observed and is often linked to drug resistance. In several cases, such heterogeneity in drug sensitivity of tumors is driven by stochastic and rever...
Reprogramming cellular identity is fundamentally at odds with replication of the genome: cell fate reprogramming requires complex multi-dimensional epigenomic changes, whereas genome replication deman...
is a human bacterial pathogen that disseminates through host tissues using a process called cell-to-cell spread. This critical yet understudied virulence strategy resembles a vesicular form of interce...
This study evaluates the effectiveness of stochastic resonance electric stimulation on neuromuscular control and proprioception in healthy and individuals with stroke.
Using the glucagon-like peptide-1 (GLP-1) antagonist exendin(9-39) and the glucose-dependent insulinotropic peptide (GIP) antagonist GIP(3-30), the purpose of this study is to clarify the ...
This is a Phase I open-label dose escalation study of a single infusion of FATE-NK100 and a short course of subcutaneous interleukin-2 (IL-2) administered after lymphodepleting chemotherap...
One of the most common and serious complications in decompensated cirrhotic patients (DCPs) is bacterial infection.The most common infections in DCPs are cases of spontaneous bacterial per...
The purpose of the study is to assess long-term side effects from subjects who receive a Fate Therapeutics genetically modified NK cell product. Subjects who previously took part in a Fate...
A subclass of LIM domain proteins that include an additional centrally-located homeodomain region that binds AT-rich sites on DNA. Many LIM-homeodomain proteins play a role as transcriptional regulators that direct cell fate.
A notch receptor and proto-oncogene protein characterized by a large extracellular domain that consists of 29 EPIDERMAL GROWTH FACTOR - like repeat sequences (EGF repeats) and five ANKYRIN REPEATS. It functions as a receptor for SERRATE-JAGGED PROTEINS and Delta1 (DLK1) protein to control cell fate determination.
Periplasmic proteins that scavenge or sense diverse nutrients. In the bacterial environment they usually couple to transporters or chemotaxis receptors on the inner bacterial membrane.
Bacterial proteins that share the property of binding irreversibly to PENICILLINS and other ANTIBACTERIAL AGENTS derived from LACTAMS. The penicillin-binding proteins are primarily enzymes involved in CELL WALL biosynthesis including MURAMOYLPENTAPEPTIDE CARBOXYPEPTIDASE; PEPTIDE SYNTHASES; TRANSPEPTIDASES; and HEXOSYLTRANSFERASES.
Genes that determine the fate of a cell or CELLS in a region of the embryo during EMBRYONIC DEVELOPMENT.