Differentiation of ciliated human midbrain-derived LUHMES neurons

Lauter, Gilbert; Coschiera, Andrea; Yoshihara, Masahito; Sugiaman-Trapman, Debora; Ezer, Sini; Sethurathinam, Shalini; Katayama, Shintaro; Kere, Juha; Swoboda, Peter

doi:10.1101/2020.06.04.134478

Cited by 5 publications

(15 citation statements)

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“…The normalized expression values of genes with multiple CAGE peaks (promoters; IFT122 and IFT140) were summed across all the peaks. The RNA-sequencing data of LUHMES differentiation was obtained from and processed as described in (Lauter et al 2020). Briefly, read counts were normalized by the sum of spike-in reads for each sample (Katayama et al 2013) and divided by the minimum non-zero value (5.78 × 10 -6 ).…”

Section: Ift122 Expression In Human Tissues and Cellsmentioning

confidence: 99%

“…As IFT122 forms the intraflagellar transport A (IFT-A) complex together with IFT144, IFT140, IFT43, IFT121 and IFT139 (Takahara et al 2018), their expression levels were also studied and found to be generally comparable in retina, chondrocyte, and osteoblast (Online Resource 5b). We further investigated the expression changes of IFT122 in Lund human mesencephalic (LUHMES) cell line which can recapitulate the neuronal cell development process in vitro (Lauter et al 2020). Here we found that IFT122 is strongly upregulated from day 2 to day 5 (Online Resource 5c), along with many other genes related to axonogenesis and ciliogenesis, indicating that IFT122 plays an important role in neuronal systems including retina.…”

Section: Ift122 Expression In Humanmentioning

confidence: 99%

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A missense variant in IFT122 associated with a canine model of retinitis pigmentosa

Kaukonen

Pettinen

Wickström³

et al. 2021

Hum Genet

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Retinitis pigmentosa (RP) is a blinding eye disease affecting nearly two million people worldwide. Dogs are affected with a similar illness termed progressive retinal atrophy (PRA). Lapponian herders (LHs) are affected with several types of inherited retinal dystrophies, and variants in PRCD and BEST1 genes have been associated with generalized PRA and canine multifocal retinopathy 3 (cmr3), respectively. However, all retinal dystrophy cases in LHs are not explained by these variants, indicating additional genetic causes of disease in the breed. We collected DNA samples from 10 PRA affected LHs, with known PRCD and BEST1 variants excluded, and 34 unaffected LHs. A genome-wide association study identified a locus on CFA20 (praw = 2.4 × 10–7, pBonf = 0.035), and subsequent whole-genome sequencing of an affected LH revealed a missense variant, c.3176G>A, in the intraflagellar transport 122 (IFT122) gene. The variant was also found in Finnish Lapphunds, in which its clinical relevancy needs to be studied further. The variant interrupts a highly conserved residue, p.(R1059H), in IFT122 and likely impairs its function. Variants in IFT122 have not been associated with retinal degeneration in mammals, but the loss of ift122 in zebrafish larvae impaired opsin transport and resulted in progressive photoreceptor degeneration. Our study establishes a new spontaneous dog model to study the role of IFT122 in RP biology, while the affected breed will benefit from a genetic test for a recessive condition.

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Section: Ift122 Expression In Human Tissues and Cellsmentioning

confidence: 99%

Section: Ift122 Expression In Humanmentioning

confidence: 99%

A missense variant in IFT122 associated with a canine model of retinitis pigmentosa

Kaukonen

Pettinen

Wickström³

et al. 2021

Hum Genet

Self Cite

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“…The sequenced STRT RNA-seq raw reads were processed as described elsewhere (Lauter et al, 2020 (Kim et al, 2019). Potential PCR duplicates were flagged with Picard MarkDuplicates.…”

Section: Strt Rna-seq Data Processingmentioning

confidence: 99%

Transient DUX4 expression induces blastomere-like expression program that is marked by SLC34A2

Yoshihara

Kirjanov

Nykänen

et al. 2021

Preprint

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DUX4 has recently been recognized as a key regulator in human embryonic genome activation (EGA). The exact role of DUX4 in human embryo is still elusive, partly due to the cytotoxicity of persistent DUX4 expression in cellular models. We report here that a transient DUX4 expression in human embryonic stem cells (hESCs) retains cell viability while inducing an EGA-like expression program in a subpopulation of the cells. These cells showed resemblance to 8-cell stage blastomeres and were thus named induced blastomere-like (iBM) cells. Trajectory inference from the single-cell RNA-seq data suggested that the expression profile of these cells progressed in a manner similar to the morula to blastocyst transition in human embryo. Finally, viable iBM cells could be enriched using an antibody against NaPi2b (SLC34A2), paving the way for further experimental approaches. The iBM cells can become a powerful tool to model transcriptional dynamics and regulation during early human embryogenesis.

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“…The normalized expression values of genes with multiple CAGE peaks (promoters; IFT122 and IFT140) were summed across all the peaks. The RNAsequencing data of LUHMES differentiation was obtained from and processed as described in (Lauter et al 2020). Brie y, read counts were normalized by the sum of spike-in reads for each sample (Katayama et al 2013) and divided by the minimum non-zero value (5.78×10 -6 ).…”

Section: Ift122 Expression In Human Tissues and Cellsmentioning

confidence: 99%

“…As IFT122 forms the intra agellar transport A (IFT-A) complex together with IFT144, IFT140, IFT43, IFT121 and IFT139 (Takahara et al 2018), their expression levels were also studied and found to be generally comparable in retina, chondrocyte, and osteoblast (Online Resource 5b). We further investigated the expression changes of IFT122 in Lund human mesencephalic (LUHMES) cell line which can recapitulate the neuronal cell development process in vitro (Lauter et al 2020). Here we found that IFT122 is strongly upregulated from day 2 to day 5 (Online Resource 5c), along with many other genes related to axonogenesis and ciliogenesis, indicating that IFT122 plays an important role in neuronal systems including retina.…”

Section: Ift122 Expression In Humanmentioning

confidence: 99%

A missense Variant in IFT122 Associated with a Canine Model of Retinitis Pigmentosa

Kaukonen

Pettinen

Wickström³

et al. 2021

Preprint

Self Cite

View full text Add to dashboard Cite

Retinitis pigmentosa (RP) is a blinding eye disease affecting nearly two million people worldwide. Dogs are affected with a similar illness termed progressive retinal atrophy (PRA). Lapponian Herders (LHs) are affected with several types of inherited retinal dystrophies, and variants in PRCD and BEST1 genes have been associated with generalized PRA and canine multifocal retinopathy 3 (cmr3), respectively. However, all retinal dystrophy cases in LHs are not explained by these variants, indicating additional genetic causes of disease in the breed. We collected DNA samples from 10 PRA-affected LHs, with known PRCD and BEST1 variants excluded, and 34 unaffected LHs. A genome-wide association study identified a locus on CFA20 (praw=2.4x10-7, pBonf=0.035), and subsequent whole-genome sequencing of an affected LH revealed a missense variant, c.3176G>A, in the intraflagellar transport 122 (IFT122) gene. The variant was also found in Finnish Lapphunds, in which its clinical relevancy needs to be studied further. The variant interrupts a highly conserved residue, p.(R1059H), in IFT122 and likely impairs its function. Variants in IFT122 have not been associated with retinal degeneration in mammals, but the loss of ift122 in zebrafish larvae impaired opsin transport and resulted in progressive photoreceptor degeneration. Our study establishes a new spontaneous dog model to study the role of IFT122 in RP biology, while the affected breed will benefit from a genetic test for a recessive condition.

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Differentiation of ciliated human midbrain-derived LUHMES neurons

Abstract: 3 4 5 Running title: Human LUHMES neurons are ciliated 6 7 8

Cited by 5 publications

References 86 publications

A missense variant in IFT122 associated with a canine model of retinitis pigmentosa

A missense variant in IFT122 associated with a canine model of retinitis pigmentosa

Transient DUX4 expression induces blastomere-like expression program that is marked by SLC34A2

A missense Variant in IFT122 Associated with a Canine Model of Retinitis Pigmentosa

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