Transcriptome analysis of human induced pluripotent stem cells derived from umbilical cord blood of ACH patient reveals potential therapy targets

Fetal skeletal dysplasia (also known as skeletal dysplasia) is one of the common congenital disabilities in clinic, which includes a series of clinical manifestations of congenital bone size and shape abnormalities, among which achondroplasia (ACH) is the most common non-fatal short limb malformation. Chondrodysplasia is characterized by short asymmetrical stature combined with skeletal malformations, and many severe skeletal complications may occur in patients of different ages. ACH is an autosomal dominant genetic disease caused by the fibroblast growth factor receptor 3 (FGFR3) gene mutation. The FGFR3 gene is a negative regulator of cartilage development. Theoretically, down-regulation of FGFR3 activity or its downstream signal may be a method to treat or alleviate ACH, and the specific treatment method remains to be explored. We have established a stable iPSC system constructed from fetal umbilical cord blood of ACH, which will lay a foundation for the exploration of the mechanism and treatment of ACH. iPSC-related information is as follows: Cell-derived cord blood, Reprogramming methods OCT4, SOX2, KLF4, cMYC and BCL-XL, Gene modification YesRelated diseases: achondroplasia, Gene/locus Gene: FGFR3 locus: 4p16.3, Mutation: c.1138G>A (p.G380R) heterozygous mutationIn order to complete the iPSC constructed from ACH umbilical cord blood as a reliable test to verify the ACH disease model, we verified whether the FGFR3 gene expression of iPSC cells constructed from ACH fetal umbilical cord blood was significantly increased through the second-generation sequencing. Three umbilical cord stem cells extracted from fetal umbilical cord blood without genetic disease were used as the control group, and the second generation sequencing was conducted to obtain the full transcriptome information. The whole genome RNA sequencing results of the ACH iPSC model expressed changes in the expression of multiple pathways related to bone development.