Transcription factor Runx1 inhibits proliferation and promotes developmental maturation in a selected population of inner olfactory nerve layer olfactory ensheathing cells

Murthy, Manjari; Bocking, Sarah; Verginelli, Federica; Stifani, Stefano

doi:10.1016/j.gene.2014.02.038

Cited by 18 publications

(16 citation statements)

References 51 publications

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“…On the other hand, little is known about Runx1 loss of function in the CNS 55 . However, increasing Runx1 protein expression inhibits the proliferation and promotes the maturation of not only olfactory ensheathing cells, non-myelinating axon-wrapping glial cells in the olfactory nerve 56 , but also microglia, although they are myeloid lineage cells, in the postnatal forebrain 57 . To the best of our knowledge, there have been no previous reports about Runx1 expression in oligodendrocyte lineage cells.…”

Section: Discussionmentioning

confidence: 99%

Quiescence of adult oligodendrocyte precursor cells requires thyroid hormone and hypoxia to activate Runx1

Tokumoto

Tamaki

Kabe

et al. 2017

Sci Rep

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The adult mammalian central nervous system (CNS) contains a population of slowly dividing oligodendrocyte precursor cells (OPCs), i.e., adult OPCs, which supply new oligodendrocytes throughout the life of animal. While adult OPCs develop from rapidly dividing perinatal OPCs, the mechanisms underlying their quiescence remain unknown. Here, we show that perinatal rodent OPCs cultured with thyroid hormone (TH) under hypoxia become quiescent and acquire adult OPCs-like characteristics. The cyclin-dependent kinase inhibitor p15/INK4b plays crucial roles in the TH-dependent cell cycle deceleration in OPCs under hypoxia. Klf9 is a direct target of TH-dependent signaling. Under hypoxic conditions, hypoxia-inducible factors mediates runt-related transcription factor 1 activity to induce G1 arrest in OPCs through enhancing TH-dependent p15/INK4b expression. As adult OPCs display phenotypes of adult somatic stem cells in the CNS, the current results shed light on environmental requirements for the quiescence of adult somatic stem cells during their development from actively proliferating stem/progenitor cells.

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Section: Discussionmentioning

confidence: 99%

Quiescence of adult oligodendrocyte precursor cells requires thyroid hormone and hypoxia to activate Runx1

Tokumoto

Tamaki

Kabe

et al. 2017

Sci Rep

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“…Specifically, decreased Runx1 levels are correlated with increased numbers of mitotic OECs, with a parallel decrease in the number of more differentiated OECs. In contrast, Runx1 overexpression results in reduced OEC proliferation (Murthy et al 2014). Thus, Runx1 contributes to the development, and possibly regeneration, of the olfactory system by acting, at least in part, to either delay or promote the proliferation-to-differentiation transition in OSN or OEC precursors, respectively.…”

Section: Runx1 Involvement In Proliferation and Developmental Maturatmentioning

confidence: 98%

“…These cells are specifically located in the inner portion of the olfactory bulb nerve layer (ONL) and exhibit characteristic molecular features, such as the expression of neuropeptide Y. In contrast, Runx1 expression is not detected in OECs that are located in the outer part of the ONL and express different sets of proteins, including the lowaffinity NGF receptor p75NTR (Murthy et al 2014). The expression of Runx1 in a particular subtype(s) of developmentally mature OECs with a specific topology and molecular profile is akin to the subtype-restricted expression of Runx1 in neuronal cells in the CNS and PNS, as discussed above.…”

Section: Runx1 Involvement In Proliferation and Developmental Maturatmentioning

confidence: 99%

Roles of Runx Genes in Nervous System Development

Wang

Stifani

2017

Advances in Experimental Medicine and Biology

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Runt-related (Runx) transcription factors play essential roles during development and adult tissue homeostasis and are responsible for several human diseases. They regulate a variety of biological mechanisms in numerous cell lineages. Recent years have seen significant progress in our understanding of the functions performed by Runx proteins in the developing and postnatal mammalian nervous system. In both central and peripheral nervous systems, Runx1 and Runx3 display remarkably specific expression in mostly non-overlapping groups of postmitotic neurons. In the central nervous system, Runx1 is involved in the development of selected motor neurons controlling neural circuits mediating vital functions such as chewing, swallowing, breathing, and locomotion. In the peripheral nervous system, Runx1 and Runx3 play essential roles during the development of sensory neurons involved in circuits mediating pain, itch, thermal sensation and sense of relative position. Runx1 and Runx3 orchestrate complex gene expression programs controlling neuronal subtype specification and axonal connectivity. Runx1 is also important in the olfactory system, where it regulates the progenitor-to-neuron transition in undifferentiated neural progenitor cells in the olfactory epithelium as well as the proliferation and developmental maturation of specific glial cells termed olfactory ensheathing cells. Moreover, upregulated Runx expression is associated with brain injury and disease. Increasing knowledge of the functions of Runx proteins in the developing and postnatal nervous system is therefore expected to improve our understanding of nervous system development, homeostasis and disease.

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“…Multiple reports have detailed a role for RUNX1 in epithelial biology [Scheitz and Tumbar, 2013]. RUNX1 has been shown to modulate developmental activation and proliferation of hair follicle stem cells and inner olfactory nerve layer olfactory ensheathing cells [Hoi et al, 2010; Lee et al, 2014; Murthy et al, 2014; Osorio et al, 2008; Osorio et al, 2011]. RUNX1 is a key regulator of the differentiation of mammary epithelium stem cells from a state of ductal and lobular bipotency [Sokol et al, 2015].…”

Section: Runx1 In Developmentmentioning

confidence: 99%

Precocious Phenotypic Transcription‐Factor Expression During Early Development

VanOudenhove

Medina

Ghule

et al. 2017

J of Cellular Biochemistry

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A novel role for phenotypic transcription factors in very early differentiation was recently observed and merits further study to elucidate what role this precocious expression may have in development. The RUNX1 transcription factor exhibits selective and transient upregulation during early mesenchymal differentiation. In contrast to phenotype-associated transcriptional control of gene expression to establish and sustain hematopoietic/myeloid lineage identity, precocious expression of RUNX1 is functionally linked to control of an epithelial to mesenchymal transition that is obligatory for development. This early RUNX1 expression spike provides a paradigm for precocious expression of a phenotypic transcription factor that invites detailed mechanistic study to fully understand its biological importance.

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Transcription factor Runx1 inhibits proliferation and promotes developmental maturation in a selected population of inner olfactory nerve layer olfactory ensheathing cells

Cited by 18 publications

References 51 publications

Quiescence of adult oligodendrocyte precursor cells requires thyroid hormone and hypoxia to activate Runx1

Quiescence of adult oligodendrocyte precursor cells requires thyroid hormone and hypoxia to activate Runx1

Roles of Runx Genes in Nervous System Development

Precocious Phenotypic Transcription‐Factor Expression During Early Development

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