Motoneurons and oligodendrocytes are sequentially generated from neural stem cells but do not appear to share common lineage-restricted progenitors in vivo

Wu, Sen; Wu, Yuanyuan; Capecchi, Mario R.

doi:10.1242/dev.02236

Cited by 167 publications

(172 citation statements)

References 42 publications

(44 reference statements)

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“…More recent studies, however, suggest that the appearance of oligodendrocyte precursors and the role of Olig2 ϩ cells are more complex. Although the ancestors to both motor neurons and oligodendrocytes transiently express Olig2, they apparently are unrelated (Mukouyama et al, 2006;Wu et al, 2006). These data are more consistent with an early segregation of neuron and glial lineages as implied by in vitro studies (Noble et al, 2004) and suggest that changes in local cell-cell interactions (Park and Appel, 2003) or expression of transcription factors upstream of Olig2 and Nkx2.2 (Zhou et al, 2001) control early cell fate choices in this region of the CNS.…”

Section: Discussionsupporting

confidence: 64%

Specification of Optic Nerve Oligodendrocyte Precursors by Retinal Ganglion Cell Axons

Gao

Miller

2006

J. Neurosci.

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Section: Discussionsupporting

confidence: 64%

Specification of Optic Nerve Oligodendrocyte Precursors by Retinal Ganglion Cell Axons

Gao

Miller

2006

J. Neurosci.

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“…This is in pronounced contrast to the multitude of lineages observed to arise from this progenitor pool during development using even the very same mouse line Masahira et al, 2006;Miyoshi et al, 2007;Ono et al, 2008) or the NG2::CreERTM T2 line (Zhu et al, 2008). Importantly, during development, the different cell types arise from distinct sets of Olig2 ϩ progenitors (e.g., Olig2 ϩ cells that generate motoneurons do not share their lineage with those that generate oligodendrocytes) (Mukouyama et al, 2006;Wu et al, 2006). Similarly, Mash1-expressing progenitors that generate neurons in the embryonic spinal cord do not share their lineage with those generating oligodendrocytes at later stages (Battiste et al, 2007).…”

Section: Progeny Of Olig2-expressing Cells In the Adult Versus Develomentioning

confidence: 91%

Progeny of Olig2-Expressing Progenitors in the Gray and White Matter of the Adult Mouse Cerebral Cortex

Dimou¹,

Simon²,

Kirchhoff³

et al. 2008

J. Neurosci.

466

548

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Despite their abundance, still little is known about the rather frequent, constantly proliferating progenitors spread throughout the adult mouse brain parenchyma. The majority of these progenitors express the basic-helix-loop-helix transcription factor Olig2, and their number further increases after injury. Here, we examine the progeny of this progenitor population by genetic fate mapping using tamoxifen-inducible Cre-recombination in the Olig2 locus to turn on permanent reporter gene expression in the adult brain. Consistent with Olig2 expression in proliferating NG2 ϩ progenitors, most reporter ϩ cells seen shortly after initiating recombination at adult stages incorporated BrdU and contained the proteoglycan NG2 in both the gray (GM) and the white matter (WM) of the cerebral cortex. However, at longer time points after induction, we observed profound differences in the identity of reporter ϩ cells in the WM and GM. Whereas most of the Olig2 ϩ progenitors had generated mature, myelinating oligodendrocytes in the WM, hardly any reporter ϩ cells showing mature oligodendrocyte characteristics were detectable even up to 6 months after recombination in the GM. In the GM, most reporter ϩ cells remained NG2 ϩ , even after injury, but stopped proliferating rather soon after recombination. Thus, our results demonstrate the continuous generation of mature, myelinating oligodendrocytes in the WM, whereas cells in the GM generated mostly postmitotic NG2 ϩ glia.

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“…To examine the consequences of ablating the candidate stem cells in the small intestine, we crossed the Bmi1-Cre-ER driver with a conditional allele encoding diphtheria toxin expressed from the Rosa26 locus 25 . Double-heterozygous mice (Bmi1 Cre-ER/+ ; Rosa26 DTA/+ ) were viable and healthy.…”

Section: Online)mentioning

confidence: 99%

Bmi1 is expressed in vivo in intestinal stem cells

2008

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Bmi1 plays an essential part in the self-renewal of hematopoietic and neural stem cells. To investigate its role in other adult stem cell populations, we generated a mouse expressing a tamoxifen-inducible Cre from the Bmi1 locus. We found that Bmi1 is expressed in discrete cells located near the bottom of crypts in the small intestine, predominantly four cells above the base of the crypt (+4 position). Over time, these cells proliferate, expand, self-renew and give rise to all the differentiated cell lineages of the small intestine epithelium. The induction of a stable form of b-catenin in these cells was sufficient to rapidly generate adenomas. Moreover, ablation of Bmi1 + cells using a Rosa26 conditional allele, expressing diphtheria toxin, led to crypt loss. These experiments identify Bmi1 as an intestinal stem cell marker in vivo. Unexpectedly, the distribution of Bmi1-expressing stem cells along the length of the small intestine suggested that mammals use more than one molecularly distinguishable adult stem cell subpopulation to maintain organ homeostasis.Adult somatic stem cells are defined by two major properties: the ability to generate more stem cells (self-renewal) and the ability to generate differentiated cell lineages 1 . To establish the presence of these two properties, the gold standard is to assess both of them in vivo and in vitro 2 . Several studies have shown in vitro that many tissues carry cells capable of selfrenewal and of giving rise to differentiated cell types. However, few experiments have clearly established in vivo self-renewal and multipotency of these cells over time 3,4 .To address this, we established a genetic fate-mapping system for stem cell populations in vivo. We chose as our target locus Bmi1, a gene already known to be involved in the selfrenewal of neuronal, hematopoietic and leukemic cells [5][6][7] . Bmi1 was first identified in a mouse proviral insertion screen for lymphomagenesis 8 . It is part of the Polycomb group gene family, and specifically a member of polycomb-repressing complex 1 (PRC1). PRC1 has an essential role in maintaining chromatin silencing 9, 10. Bmi1 −/− mice die before or near weaning from a defect in self-renewal of hematopoietic stem cells 11,12 . Our hypothesis was that PRC1 might be part of a general mechanism for maintaining self-renewal in various adult stem cell populations.We inserted a construct encoding a internal ribosome entry site (IRES)-Cre-estrogen receptor binding domain fusion (IRES-Cre-ER) into the 3′ untranslated region of Bmi1 ( Supplementary Fig. 1 To evaluate the repopulation kinetics of the crypt cells derived from Bmi1 + parents, we analyzed the small intestines of Bmi1 Cre-ER/+ ;Rosa26 LacZ/+ mice from day 2 to day 30 after tamoxifen induction, analyzing and following crypts on serial adjacent sections. Crypts with LacZ + cells presented a large variation in the number of stained cells. From day 2 to day 30, there was a continual increase in the number of cells labeled per crypt . Over time, the number of crypts th...

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Motoneurons and oligodendrocytes are sequentially generated from neural stem cells but do not appear to share common lineage-restricted progenitors in vivo

Cited by 167 publications

References 42 publications

Specification of Optic Nerve Oligodendrocyte Precursors by Retinal Ganglion Cell Axons

Specification of Optic Nerve Oligodendrocyte Precursors by Retinal Ganglion Cell Axons

Progeny of Olig2-Expressing Progenitors in the Gray and White Matter of the Adult Mouse Cerebral Cortex

Bmi1 is expressed in vivo in intestinal stem cells

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