Fibrinogen induces neural stem cell differentiation into astrocytes in the subventricular zone via BMP signaling

Pous, Lauriane; Deshpande, Sachin S.; Nath, Suvra; Mezey, Szilvia; Malik, Subash C.; Schildge, Sebastian; Bohrer, Christian; Topp, Könül; Pfeifer, Dietmar; Fernández-Klett, Francisco; Doostkam, Soroush; Galanakis, Dennis K.; Taylor, Verdon; Akassoglou, Katerina; Schachtrup, Christian

doi:10.1038/s41467-020-14466-y

Cited by 61 publications

(79 citation statements)

References 68 publications

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“…Interestingly, BMP and Notch signaling are also induced after injury in mouse, but in contrast to zebrafish they induce glial cell fate (Bohrer et al, 2015;Pous et al, 2020). Accordingly, in the injured mouse brain, the progeny of SVZ NSCs will not migrate to the OB to differentiate into neurons, but instead these cells are recruited to the injury site where they differentiate into glia and participate in the formation of a glial scar, which will subsequently repress neural regeneration (Goings et al, 2004;Wang et al, 2018).…”

Section: Responses To Traumatic Brain Injury In Mousementioning

confidence: 99%

“…Accordingly, in the injured mouse brain, the progeny of SVZ NSCs will not migrate to the OB to differentiate into neurons, but instead these cells are recruited to the injury site where they differentiate into glia and participate in the formation of a glial scar, which will subsequently repress neural regeneration (Goings et al, 2004;Wang et al, 2018). It was shown in mouse that upon traumatic brain injury and consequent vascular rupture, the coagulation factor Fibrinogen is released into the SVZ where it activates BMP signaling and increases the expression of its direct downstream mediator Id3 (Pous et al, 2020). Injury-induced up-regulation of Id3 by BMP2 in the SVZ promotes astrogenesis over neurogenesis by positively regulating the expression of astrocyte specific genes such as GFAP, GLAST, and Aldh1l1.…”

Section: Responses To Traumatic Brain Injury In Mousementioning

confidence: 99%

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Common and Distinct Features of Adult Neurogenesis and Regeneration in the Telencephalon of Zebrafish and Mammals

et al. 2020

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In contrast to mammals, the adult zebrafish brain shows neurogenic activity in a multitude of niches present in almost all brain subdivisions. Irrespectively, constitutive neurogenesis in the adult zebrafish and mouse telencephalon share many similarities at the cellular and molecular level. However, upon injury during tissue repair, the situation is entirely different. In zebrafish, inflammation caused by traumatic brain injury or by induced neurodegeneration initiates specific and distinct neurogenic programs that, in combination with signaling pathways implicated in constitutive neurogenesis, quickly, and efficiently overcome the loss of neurons. In the mouse brain, injuryinduced inflammation promotes gliosis leading to glial scar formation and inhibition of regeneration. A better understanding of the regenerative mechanisms occurring in the zebrafish brain could help to develop new therapies to combat the debilitating consequences of brain injury, stroke, and neurodegeneration. The aim of this review is to compare the properties of neural progenitors and the signaling pathways, which control adult neurogenesis and regeneration in the zebrafish and mammalian telencephalon.

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Section: Responses To Traumatic Brain Injury In Mousementioning

confidence: 99%

Section: Responses To Traumatic Brain Injury In Mousementioning

confidence: 99%

Common and Distinct Features of Adult Neurogenesis and Regeneration in the Telencephalon of Zebrafish and Mammals

et al. 2020

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“…HA and perlecan in this niche environment also promote neuron proliferation and differentiation through FGF-2 cell signalling [ 7 , 8 , 9 ]. Fibrinogen is a specific ligand for SVZ niche HA and triggers astrogliogenesis following corticol brain injury through BMP signalling [ 267 , 268 ]. Fibrinogen inhibits neuronal differentiation in the SVZ niche while it promotes astrogliogenesis via activation of BMP cell signalling.…”

Section: Ecm Components Influence Cell Migration During Neural Development and Cns Repairmentioning

confidence: 99%

The CNS/PNS Extracellular Matrix Provides Instructive Guidance Cues to Neural Cells and Neuroregulatory Proteins in Neural Development and Repair

Melrose

Hayes

Bix

2021

IJMS

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Background. The extracellular matrix of the PNS/CNS is unusual in that it is dominated by glycosaminoglycans, especially hyaluronan, whose space filling and hydrating properties make essential contributions to the functional properties of this tissue. Hyaluronan has a relatively simple structure but its space-filling properties ensure micro-compartments are maintained in the brain ultrastructure, ensuring ionic niches and gradients are maintained for optimal cellular function. Hyaluronan has cell-instructive, anti-inflammatory properties and forms macro-molecular aggregates with the lectican CS-proteoglycans, forming dense protective perineuronal net structures that provide neural and synaptic plasticity and support cognitive learning. Aims. To highlight the central nervous system/peripheral nervous system (CNS/PNS) and its diverse extracellular and cell-associated proteoglycans that have cell-instructive properties regulating neural repair processes and functional recovery through interactions with cell adhesive molecules, receptors and neuroregulatory proteins. Despite a general lack of stabilising fibrillar collagenous and elastic structures in the CNS/PNS, a sophisticated dynamic extracellular matrix is nevertheless important in tissue form and function. Conclusions. This review provides examples of the sophistication of the CNS/PNS extracellular matrix, showing how it maintains homeostasis and regulates neural repair and regeneration.

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“… 14 , 19 Fibrinogen activates bone morphogenetic protein (BMP) receptor signalling in OPCs and neural precursor cells to inhibit remyelination and neurogenesis, respectively. 14 , 20 Fibrinogen induces a cell fate switch of NG2 + (encoded by CSPG4 ) OPCs to astrocytes via BMP receptor activation, 14 suggesting a role for fibrinogen in the extrinsic inhibition of remyelination by inducing OPC-derived astrogenesis in the neurovascular niche. Furthermore, when fibrinogen is converted to fibrin, it induces oxidative stress and pro-inflammatory polarization of microglia and macrophages, 21 , 22 which is toxic to OPCs and contributes to remyelination failure.…”

Section: Introductionmentioning

confidence: 99%

BMP receptor blockade overcomes extrinsic inhibition of remyelination and restores neurovascular homeostasis

Petersen

Tognatta

Meyer-Franke

et al. 2021

Brain

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Extrinsic inhibitors at sites of blood–brain barrier disruption and neurovascular damage contribute to remyelination failure in neurological diseases. However, therapies to overcome the extrinsic inhibition of remyelination are not widely available and the dynamics of glial progenitor niche remodeling at sites of neurovascular dysfunction are largely unknown. By integrating in vivo two-photon imaging co-registered with electron microscopy and transcriptomics in chronic neuroinflammatory lesions, we found that oligodendrocyte precursor cells clustered perivascularly at sites of limited remyelination with deposition of fibrinogen, a blood coagulation factor abundantly deposited in multiple sclerosis lesions. By developing a screen (OPC-X-screen) to identify compounds that promote remyelination in the presence of extrinsic inhibitors, we showed that known promyelinating drugs did not rescue the extrinsic inhibition of remyelination by fibrinogen. In contrast, bone morphogenetic protein type I receptor blockade rescued the inhibitory fibrinogen effects and restored a promyelinating progenitor niche by promoting myelinating oligodendrocytes, while suppressing astrocyte cell fate, with potent therapeutic effects in chronic models of multiple sclerosis. Thus, abortive oligodendrocyte precursor cell differentiation by fibrinogen is refractory to known promyelinating compounds, suggesting that blockade of the bone morphogenetic protein signalling pathway may enhance remyelinating efficacy by overcoming extrinsic inhibition in neuroinflammatory lesions with vascular damage.

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Fibrinogen induces neural stem cell differentiation into astrocytes in the subventricular zone via BMP signaling

Cited by 61 publications

References 68 publications

Common and Distinct Features of Adult Neurogenesis and Regeneration in the Telencephalon of Zebrafish and Mammals

Common and Distinct Features of Adult Neurogenesis and Regeneration in the Telencephalon of Zebrafish and Mammals

The CNS/PNS Extracellular Matrix Provides Instructive Guidance Cues to Neural Cells and Neuroregulatory Proteins in Neural Development and Repair

BMP receptor blockade overcomes extrinsic inhibition of remyelination and restores neurovascular homeostasis

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