Complementary patterns of gene expression by human oligodendrocyte progenitors and their environment predict determinants of progenitor maintenance and differentiation

Sim, Fraser J.; Lang, Jennifer K.; Waldau, Ben; Roy, Neeta S.; Schwartz, Theodore; Pilcher, Webster H.; Chandross, Karen J.; Natesan, Sridaran; Merrill, Jean E.; Goldman, Steven A.

doi:10.1002/ana.20812

Cited by 137 publications

(134 citation statements)

References 57 publications

(64 reference statements)

Supporting

Mentioning

123

Contrasting

Unclassified

Order By: Relevance

“…Interestingly, the soluble form of PTPRZ is responsible for mediating the differentiation of OPCs, indicating that this molecule participates in myelination and thus represents an avenue of treatment for demyelinating lesions. In particular, it will be critical to test the effect of soluble PTPRZ on human white matter glial progenitor cells, as Sim et al reported an increase in the number of O4 + cells in cells treated with PTPRZ siRNA (19). This increase was accompanied by a reduction in the number of proliferating glial cells expressing the A2B5 antigen, indicating that PTPRZ could inhibit human oligodendrocyte differentiation.…”

Section: Discussionmentioning

confidence: 99%

A complex between contactin-1 and the protein tyrosine phosphatase PTPRZ controls the development of oligodendrocyte precursor cells

Lamprianou

Chatzopoulou

Thomas

et al. 2011

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

View full text Add to dashboard Cite

The six members of the contactin (CNTN) family of neural cell adhesion molecules are involved in the formation and maintenance of the central nervous system (CNS) and have been linked to mental retardation and neuropsychiatric disorders such as autism. Five of the six CNTNs bind to the homologous receptor protein tyrosine phosphatases gamma (PTPRG) and zeta (PTPRZ), but the biological roles of these interactions remain unclear. We report here the cocrystal structure of the carbonic anhydrase-like domain of PTPRZ bound to tandem Ig repeats of CNTN1 and combine these structural data with binding assays to show that PTPRZ binds specifically to CNTN1 expressed at the surface of oligodendrocyte precursor cells. Furthermore, analyses of glial cell populations in wild-type and PTPRZ-deficient mice show that the binding of PTPRZ to CNTN1 expressed at the surface of oligodendrocyte precursor cells inhibits their proliferation and promotes their development into mature oligodendrocytes. Overall, these results implicate the PTPRZ/CNTN1 complex as a previously unknown modulator of oligodendrogenesis.

show abstract

Section: Discussionmentioning

confidence: 99%

A complex between contactin-1 and the protein tyrosine phosphatase PTPRZ controls the development of oligodendrocyte precursor cells

Lamprianou

Chatzopoulou

Thomas

et al. 2011

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

View full text Add to dashboard Cite

show abstract

“…[52][53][54][55][56] PTPRZ1 gene products are expressed from early developmental to adulthood in glial cells 47,[57][58][59] as well as in certain population of neurons [60][61][62][63] and are implicated in neuron-glial cell interactions that involve on bi-directional signaling, including myelination and node of Ranvier formation, through interactions with neuronal cell adhesion molecules. 55,56 Interestingly, in situ hybridization analysis has shown that PTPRZ1 is expressed in the subventricular zone of the lateral ventricles in early embryos and in adults, in the subgranular zone in the dentate gyrus of the hippocampus of adults, 57,64 and in adult glial progenitor cells, 65 suggesting that PTPRZ1 also has a function in adult stem/progenitor cells. In addition, it has been shown that inhibition of PTPRZ1 expression or inhibition of RPTPb activity in adult glial progenitors leads to their differentiation into mature oligodendrocytes, 65 supporting a role for RPTPb activity in the maintenance of glial progenitors in an undifferentiated state.…”

Section: Discussionmentioning

confidence: 99%

“…55,56 Interestingly, in situ hybridization analysis has shown that PTPRZ1 is expressed in the subventricular zone of the lateral ventricles in early embryos and in adults, in the subgranular zone in the dentate gyrus of the hippocampus of adults, 57,64 and in adult glial progenitor cells, 65 suggesting that PTPRZ1 also has a function in adult stem/progenitor cells. In addition, it has been shown that inhibition of PTPRZ1 expression or inhibition of RPTPb activity in adult glial progenitors leads to their differentiation into mature oligodendrocytes, 65 supporting a role for RPTPb activity in the maintenance of glial progenitors in an undifferentiated state. Using experimental allergic encephalomyelitis (EAE), an inducible mouse model for multiple sclerosis (MS), PTPRZ1-deficient mice could not repair EAE lesions, although PTPRZ1 expression is increased in human remyelinating oligodendrocytes of MS biopsies.…”

Section: Discussionmentioning

confidence: 99%

Molecular dissection of NRG1-ERBB4 signaling implicates PTPRZ1 as a potential schizophrenia susceptibility gene

et al. 2007

View full text Add to dashboard Cite

Neuregulin and the neuregulin receptor ERBB4 have been genetically and functionally implicated in schizophrenia. In this study, we used the yeast two-hybrid system to identify proteins that interact with ERBB4, to identify genes and pathways that might contribute to schizophrenia susceptibility. We identified the MAGI scaffolding proteins as ERBB4-binding proteins. After validating the interaction of MAGI proteins with ERBB4 in mammalian cells, we demonstrated that ERBB4 expression, alone or in combination with ERBB2 or ERBB3, led to the tyrosine phosphorylation of MAGI proteins, and that this could be further enhanced with receptor activation by neuregulin. As MAGI proteins were previously shown to interact with receptor phosphotyrosine phosphatase b/f (RPTPb), we postulated that simultaneous binding of MAGI proteins to RPTPb and ERBB4 forms a phosphotyrosine kinase/phosphotyrosine phosphatase complex. Studies in cultured cells confirmed both a spatial and functional association between ERBB4, MAGI and RPTPb. Given the evidence for this functional association, we examined the genes coding for MAGI and RPTPb for genetic association with schizophrenia in a Caucasian United Kingdom case-control cohort (n = B1400). PTPRZ1, which codes for RPTPb, showed significant, gene-wide and hypothesis-wide association with schizophrenia in our study (best individual single-nucleotide polymorphism allelic P = 0.0003; gene-wide P = 0.0064; hypothesiswide P = 0.026). The data provide evidence for a role of PTPRZ1, and for RPTPb signaling abnormalities, in the etiology of schizophrenia. Furthermore, the data indicate a role for RPTPb in the modulation of ERBB4 signaling that may in turn provide further support for an important role of neuregulin/ERBB4 signaling in the molecular basis of schizophrenia.

show abstract

“…The CDS was then transferred into pTRIP-EF1α by replacing mCherry using unique restriction sites (Table S3). Lentiviruses were prepared as described previously (44). In brief, after triple transfection of HEK 293T cells with pTRIP and packaging plasmids pLP/VSVG (Life Technologies) and psPAX2 (AddGene), viral supernatant was collected at 48 and 72 h. Titration of virus was performed on matched mCherryexpressing virus using flow cytometry for mCherry fluorescence and directly compared with TF viruses using qPCR for the WPRE sequence (45).…”

Section: Methodsmentioning

confidence: 99%

Transcription factor induction of human oligodendrocyte progenitor fate and differentiation

Wang

Pol

Haberman

et al. 2014

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

Self Cite

View full text Add to dashboard Cite

Human oligodendrocyte progenitor cell (OPC) specification and differentiation occurs slowly and limits the potential for cell-based treatment of demyelinating disease. In this study, using FACS-based isolation and microarray analysis, we identified a set of transcription factors expressed by human primary CD140a + O4 + OPCs relative to CD133 + CD140a − neural stem/progenitor cells (NPCs). Among these, lentiviral overexpression of transcription factors ASCL1, SOX10, and NKX2.2 in NPCs was sufficient to induce Sox10 enhancer activity, OPC mRNA, and protein expression consistent with OPC fate; however, unlike ASCL1 and NKX2.2, only the transcriptome of SOX10-infected NPCs was induced to a human OPC gene expression signature. Furthermore, only SOX10 promoted oligodendrocyte commitment, and did so at quantitatively equivalent levels to native OPCs. In xenografts of shiverer/rag2 animals, SOX10 increased the rate of mature oligodendrocyte differentiation and axon ensheathment. Thus, SOX10 appears to be the principle and rate-limiting regulator of myelinogenic fate from human NPCs.neural precursor cell | transplantation | reprogramming

show abstract

Complementary patterns of gene expression by human oligodendrocyte progenitors and their environment predict determinants of progenitor maintenance and differentiation

Abstract: The RTPZ and BMP pathways regulate the self-maintenance of adult human WMPCs, and can be modulated to induce their oligodendrocytic or astrocytic differentiation. As such, they provide targets by which to productively mobilize resident progenitor cells of the adult human brain.

Cited by 137 publications

References 57 publications

A complex between contactin-1 and the protein tyrosine phosphatase PTPRZ controls the development of oligodendrocyte precursor cells

A complex between contactin-1 and the protein tyrosine phosphatase PTPRZ controls the development of oligodendrocyte precursor cells

Molecular dissection of NRG1-ERBB4 signaling implicates PTPRZ1 as a potential schizophrenia susceptibility gene

Transcription factor induction of human oligodendrocyte progenitor fate and differentiation

Contact Info

Product

Resources

About