Generation and characterisation of four human NAD(P)HX epimerase (NAXE) knockout iPSC lines
Pathogenic variants in NAD(P)HX epimerase (NAXE) cause early-onset progressive encephalopathy with brain edema and/or leukoencephalopathy-1 (PEBEL1), an ultra-rare severe neurometabolic disorder resulting in death in infancy. The absence of functional NAD(P)HX epimerase leads to accumulation of S- a...
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| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2025-09-01
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| Series: | Stem Cell Research |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1873506125001321 |
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| author | Tim Sikora Myrto Patraskaki Sara Howden Alison Graham John Christodoulou Carole L. Linster Nicole J. Van Bergen |
| author_facet | Tim Sikora Myrto Patraskaki Sara Howden Alison Graham John Christodoulou Carole L. Linster Nicole J. Van Bergen |
| author_sort | Tim Sikora |
| collection | DOAJ |
| description | Pathogenic variants in NAD(P)HX epimerase (NAXE) cause early-onset progressive encephalopathy with brain edema and/or leukoencephalopathy-1 (PEBEL1), an ultra-rare severe neurometabolic disorder resulting in death in infancy. The absence of functional NAD(P)HX epimerase leads to accumulation of S- and R-forms of NAD(P)HX, inhibiting key metabolic pathways. We have generated four NAXE-deficient cell lines via simultaneous CRISPR/Cas9-mediated gene knockout (KO) of NAXE and episomal reprogramming of control human fibroblasts into induced pluripotent stem cells (iPSCs). We have demonstrated loss of NAXE gene expression, characterized iPSC pluripotency and differentiation potential into three germ layers. This provides a suitable model for investigating disease mechanisms and therapies. |
| format | Article |
| id | doaj-art-49c52aa43e7449b8ac5f9cc115bc1488 |
| institution | Kabale University |
| issn | 1873-5061 |
| language | English |
| publishDate | 2025-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Stem Cell Research |
| spelling | doaj-art-49c52aa43e7449b8ac5f9cc115bc14882025-08-20T03:58:00ZengElsevierStem Cell Research1873-50612025-09-018710378210.1016/j.scr.2025.103782Generation and characterisation of four human NAD(P)HX epimerase (NAXE) knockout iPSC linesTim Sikora0Myrto Patraskaki1Sara Howden2Alison Graham3John Christodoulou4Carole L. Linster5Nicole J. Van Bergen6Murdoch Children’s Research Institute, Parkville, Victoria, Australia; Department of Paediatrics, University of Melbourne, Parkville, Victoria, AustraliaLuxembourg Centre for Systems Biomedicine, L-4362 Esch-sur-Alzette, LuxembourgMurdoch Children’s Research Institute, Parkville, Victoria, AustraliaMurdoch Children’s Research Institute, Parkville, Victoria, AustraliaMurdoch Children’s Research Institute, Parkville, Victoria, Australia; Department of Paediatrics, University of Melbourne, Parkville, Victoria, AustraliaLuxembourg Centre for Systems Biomedicine, L-4362 Esch-sur-Alzette, LuxembourgMurdoch Children’s Research Institute, Parkville, Victoria, Australia; Department of Paediatrics, University of Melbourne, Parkville, Victoria, Australia; Corresponding author at: Murdoch Children's Research Institute, 50 Flemington Road, Parkville, Victoria 3052 Australia.Pathogenic variants in NAD(P)HX epimerase (NAXE) cause early-onset progressive encephalopathy with brain edema and/or leukoencephalopathy-1 (PEBEL1), an ultra-rare severe neurometabolic disorder resulting in death in infancy. The absence of functional NAD(P)HX epimerase leads to accumulation of S- and R-forms of NAD(P)HX, inhibiting key metabolic pathways. We have generated four NAXE-deficient cell lines via simultaneous CRISPR/Cas9-mediated gene knockout (KO) of NAXE and episomal reprogramming of control human fibroblasts into induced pluripotent stem cells (iPSCs). We have demonstrated loss of NAXE gene expression, characterized iPSC pluripotency and differentiation potential into three germ layers. This provides a suitable model for investigating disease mechanisms and therapies.http://www.sciencedirect.com/science/article/pii/S1873506125001321 |
| spellingShingle | Tim Sikora Myrto Patraskaki Sara Howden Alison Graham John Christodoulou Carole L. Linster Nicole J. Van Bergen Generation and characterisation of four human NAD(P)HX epimerase (NAXE) knockout iPSC lines Stem Cell Research |
| title | Generation and characterisation of four human NAD(P)HX epimerase (NAXE) knockout iPSC lines |
| title_full | Generation and characterisation of four human NAD(P)HX epimerase (NAXE) knockout iPSC lines |
| title_fullStr | Generation and characterisation of four human NAD(P)HX epimerase (NAXE) knockout iPSC lines |
| title_full_unstemmed | Generation and characterisation of four human NAD(P)HX epimerase (NAXE) knockout iPSC lines |
| title_short | Generation and characterisation of four human NAD(P)HX epimerase (NAXE) knockout iPSC lines |
| title_sort | generation and characterisation of four human nad p hx epimerase naxe knockout ipsc lines |
| url | http://www.sciencedirect.com/science/article/pii/S1873506125001321 |
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