Coordinated control of terminal differentiation and restriction of cellular plasticity
نویسندگان
چکیده
The acquisition of a specific cellular identity is usually paralleled by a restriction of cellular plasticity. Whether and how these two processes are coordinated is poorly understood. Transcription factors called terminal selectors activate identity-specific effector genes during neuronal differentiation to define the structural and functional properties of a neuron. To study restriction of plasticity, we ectopically expressed C. elegans CHE-1, a terminal selector of ASE sensory neuron identity. In undifferentiated cells, ectopic expression of CHE-1 results in activation of ASE neuron type-specific effector genes. Once cells differentiate, their plasticity is restricted and ectopic expression of CHE-1 no longer results in activation of ASE effector genes. In striking contrast, removal of the respective terminal selectors of other sensory, inter-, or motor neuron types now enables ectopically expressed CHE-1 to activate its ASE-specific effector genes, indicating that terminal selectors not only activate effector gene batteries but also control the restriction of cellular plasticity. Terminal selectors mediate this restriction at least partially by organizing chromatin. The chromatin structure of a CHE-1 target locus is less compact in neurons that lack their resident terminal selector and genetic epistasis studies with H3K9 methyltransferases suggest that this chromatin modification acts downstream of a terminal selector to restrict plasticity. Taken together, terminal selectors activate identity-specific genes and make non-identity-defining genes less accessible, thereby serving as a checkpoint to coordinate identity specification with restriction of cellular plasticity.
منابع مشابه
High neuronal/astroglial differentiation plasticity of adult rat hippocampal neural stem/progenitor cells in response to the effects of embryonic and adult cerebrospinal fluids
Hippocampal neural stem/progenitor cells (hipp-NS/PCs) of the adult mammalian brain are important sources of neuronal and gial cell production. In this study, the main goal is to investigate the plasticity of these cells in neuronal/astroglial differentiations. To this end, the differentiation of the hipp-NS/PCs isolated from 3-month-old Wistar rats was investigated in response to the embryonic...
متن کاملReprogramming by cytosolic extract of human embryonic stem cells improves dopaminergic differentiation potential of human adipose tissue-derived stem cells
The extract of pluripotent stem cells induces dedifferentiation of somatic cells with restricted plasticity. In this study, we used the extract of human embryonic stem cells (hESC) to dedifferentiate adipose tissue-derived stem cells (ADSCs) and examined the impact of this reprogramming event on dopaminergic differentiation of the cells. For this purpose, cytoplasmic extract of ESCs was prepare...
متن کاملMsx homeobox genes inhibit differentiation through upregulation of cyclin D1.
During development, patterning and morphogenesis of tissues are intimately coordinated through control of cellular proliferation and differentiation. We describe a mechanism by which vertebrate Msx homeobox genes inhibit cellular differentiation by regulation of the cell cycle. We show that misexpression of Msx1 via retroviral gene transfer inhibits differentiation of multiple mesenchymal and e...
متن کاملImplementing the New First and Second Differentiation of a General Yield Surface in Explicit and Implicit Rate-Independent Plasticity
In the current research with novel first and second differentiations of a yield function, Euler forward along with Euler backward with its consistent elastic-plastic modulus are newly implemented in finite element program in rate-independent plasticity. An elastic-plastic internally pressurized thick walled cylinder is analyzed with four famous criteria including both pressure dependent and ind...
متن کاملDistribution of Specific Glycoconjugates in Early Mouse Embryonic Notochord and Paraxial Mesenchyme
It is well known that glycoconjugate components of the cell surface and extracellular matrix, play an essential role(s) in many developmental phenomena such as cell differentiation, migration, and cellular interactions. The purpose of this study was to investigate distribution of this macromolecules during differentiation of the notochord and paraxial mesoderm. Formalin fixed paraffin sections ...
متن کامل