Fertile offspring from sterile sex chromosome trisomic mice.
Takayuki HirotaHiroshi OhtaBenjamin E PowellShantha K MahadevaiahObah A OjarikreMitinori SaitouJames M A TurnerPublished in: Science (New York, N.Y.) (2017)
Having the correct number of chromosomes is vital for normal development and health. Sex chromosome trisomy affects 0.1% of the human population and is associated with infertility. We show that during reprogramming to induced pluripotent stem cells (iPSCs), fibroblasts from sterile trisomic XXY and XYY mice lose the extra sex chromosome through a phenomenon we term trisomy-biased chromosome loss (TCL). Resulting euploid XY iPSCs can be differentiated into the male germ cell lineage and functional sperm that can be used in intracytoplasmic sperm injection to produce chromosomally normal, fertile offspring. Sex chromosome loss is comparatively infrequent during mouse XX and XY iPSC generation. TCL also applies to other chromosomes, generating euploid iPSCs from cells of a Down syndrome mouse model. It can also create euploid iPSCs from human trisomic patient fibroblasts. The findings have relevance to overcoming infertility and other trisomic phenotypes.
Keyphrases
- induced pluripotent stem cells
- copy number
- mouse model
- germ cell
- public health
- healthcare
- high fat diet
- induced apoptosis
- high fat diet induced
- endothelial cells
- preterm infants
- metabolic syndrome
- type diabetes
- case report
- gene expression
- climate change
- cell death
- health information
- insulin resistance
- social media
- health promotion