Induced expression of Olig2 is sufficient for oligodendrocyte specification but not for motoneuron specification and astrocyte repression

Du, Zhong Wei; Li, Xue Jun; Nguyen, Giang Dang; Zhang, Su Chun

doi:10.1016/j.mcn.2006.08.007

Cited by 49 publications

(45 citation statements)

References 37 publications

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“…These in vitro observations are consistent with the fact that NC cells are responsive to BMPs, because BMPs are known to regulate NC formation and delamination (33,34). They also highlight that antagonizing BMP signaling with Noggin in BC derivatives in vitro contributes to the loss of NC characteristics and acquisition of CNS phenotypes.…”

Section: Discussionsupporting

confidence: 74%

Boundary cap cells are peripheral nervous system stem cells that can be redirected into central nervous system lineages

Zujovic

Thibaud

Bachelin

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

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Boundary cap cells (BC), which express the transcription factor Krox20, participate in the formation of the boundary between the central nervous system and the peripheral nervous system. To study BC stemness, we developed a method to purify and amplify BC in vitro from Krox20Cre/+ , R26RYFP/+ mouse embryos. We show that BC progeny are EGF/FGF2-responsive, form spheres, and express neural crest markers. Upon growth factor withdrawal, BC progeny gave rise to multiple neural crest and CNS lineages. Transplanted into the developing murine forebrain, they successfully survived, migrated, and integrated within the host environment. Surprisingly, BC progeny generated exclusively CNS cells, including neurons, astrocytes, and myelin-forming oligodendrocytes. In vitro experiments indicated that a sequential combination of ventralizing morphogens and glial growth factors was necessary to reprogram BC into oligodendrocytes. Thus, BC progeny are endowed with differentiation plasticity beyond the peripheral nervous system. The demonstration that CNS developmental cues can reprogram neural crest-derived stem cells into CNS derivatives suggests that BC could serve as a source of cell type-specific lineages, including oligodendrocytes, for cell-based therapies to treat CNS disorders.dysmyelination | reprogramming | transplantation B oundary cap cells (BC) are neural crest (NC) derivatives and were first described as discrete cell clusters localized at the dorsal root entry zone and motor exit point of the embryonic spinal cord (1). Their specific location at the central nervous system (CNS) and peripheral nervous system (PNS) interface and genetic ablation (2) showed that BC are involved in the formation of PNS-CNS boundaries. BC maintain spinal cord integrity by inhibiting motoneuron cell bodies exit to the periphery (3). Fate mapping, based on the exclusive expression of the zinc finger transcription factor Krox20 by BC between embryonic day (E)10.5 and E15.5, showed that migrating BC derivatives differentiate into Schwann cells (SC) in spinal roots, and satellite cells and a subset of nociceptive neurons in dorsal root ganglia (DRG), suggesting their multipotency (2). HjerlingLeffler and collaborators (4) highlighted the presence of a pluripotent population in the E11 mouse DRG capable of selfrenewal and differentiation into multiple NC derivatives. We reported that BC have a defined molecular signature intermediate between NC cells and SC precursors (3). Furthermore, when transplanted remotely from a focal myelin lesion of the spinal cord, BC generated remyelinating SC and few oligodendrocytes. Overall, these results strongly suggest that BC are stem cells of the embryonic PNS. However, the definition of BC stemness has been hampered by the difficulty of purifying and amplifying this restricted population. In this study, we used cellfate mapping, FACS, and microdissection to isolate, expand, and assess BC stemness in vitro and in vivo. Our data show that BC progeny behave as stem cells that can acquire differentiation plasti...

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Section: Discussionsupporting

confidence: 74%

Boundary cap cells are peripheral nervous system stem cells that can be redirected into central nervous system lineages

Zujovic

Thibaud

Bachelin

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

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“…Dissimilarity also exists during the transition from pre-OPCs into OPCs. When differentiating mESCs into OPCs, FGF2 is able to convert the Olig2-expressing cells into OPCs efficiently (Du et al, 2006). For differentiation of human oligodendrocytes, the presence of FGF2 in cultures promote the generation of pre-OPCs from Olig2-expressing cells, however, these pre-OPCs will not convert into OPCs if FGF2 is presented in the culture (Hu et al, 2009a).…”

Section: Distinctive Neural Differentiation Of Human Pscsmentioning

confidence: 99%

Specification of functional neurons and glia from human pluripotent stem cells

Jiang

Zhang

2012

Protein Cell

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Human pluripotent stem cells (PSCs) such as embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) hold great promise in regenerative medicine as they are an important source of functional cells for potential cell replacement. These human PSCs, similar to their counterparts of mouse, have the full potential to give rise to any type of cells in the body. However, for the promise to be fulfilled, it is necessary to convert these PSCs into functional specialized cells. Using the developmental principles of neural lineage specification, human ESCs and iPSCs have been effectively differentiated to regional and functional specific neurons and glia, such as striatal gama-aminobutyric acid (GABA)-ergic neurons, spinal motor neurons and myelin sheath forming oligodendrocytes. The human PSCs, in general differentiate after the similar developmental program as that of the mouse: they use the same set of cell signaling to tune the cell fate and they share a conserved transcriptional program that directs the cell fate transition. However, the human PSCs, unlike their counterparts of mouse, tend to respond divergently to the same set of extracellular signals at certain stages of differentiation, which will be a critical consideration to translate the animal model based studies to clinical application.

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“…103 In a mouse embryonic stem (ES) cell line, Olig2 requires the cooperation of retinoic acid (RA) and Shh for motor neuron specification. 104 Olig2 bypasses the need of Shh in oligodendrocyte specification but can not bypass the CNTF-STAT signaling to repress astrocyte differentiation. 104 Unlike Olig2 that seems essential for oligodendrocyte development, initial evidence indicates a redundant, non-essential function for Olig1.…”

Section: Mechanisms For Timing Neural Specificationmentioning

confidence: 99%

“…104 Olig2 bypasses the need of Shh in oligodendrocyte specification but can not bypass the CNTF-STAT signaling to repress astrocyte differentiation. 104 Unlike Olig2 that seems essential for oligodendrocyte development, initial evidence indicates a redundant, non-essential function for Olig1. 105 However, more recent work with the Olig1 mutant mice questions the previous data and suggests that Olig1 is, in fact, a central regulator of oligodendrocyte maturation and myelinogenesis.…”

Section: Mechanisms For Timing Neural Specificationmentioning

confidence: 99%

Dynamic signaling for neural stem cell fate determination

Wen

Liu

2009

Cell Adhesion & Migration

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Central nervous system (CNS) development starts from neural stem cells (NSCs) which ultimately give rise to the three major cell types (neurons, oligodendrocytes and astrocytes) of the CNS. NSCs are specified in space-and time-related fashions, becoming spatially heterogeneous and generating a progressively restricted repertoire of cell types. Mammalian NSCs produce different cell types at different time points during development under the influence of multiple signaling pathways. These pathways act in a dynamic web mode to determine the fate of NSCs via modulating the expression and activity of distinct set of transcription factors which in turn trigger the transcription of neural fate-associated genes. This review thus introduces the major signal pathways, transcription factors and their cross-talks and coordinative interactions in NSC fate determination.

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Induced expression of Olig2 is sufficient for oligodendrocyte specification but not for motoneuron specification and astrocyte repression

Cited by 49 publications

References 37 publications

Boundary cap cells are peripheral nervous system stem cells that can be redirected into central nervous system lineages

Boundary cap cells are peripheral nervous system stem cells that can be redirected into central nervous system lineages

Specification of functional neurons and glia from human pluripotent stem cells

Dynamic signaling for neural stem cell fate determination

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