Stem Cell Lamin A

The causal agent in hgps is the progerin protein an aberrant form of the nuclear architectural protein lamin a 1 2 8 progerin is generated by a heterozygous c1824t mutation in the lmna gene which activates a cryptic splice site and gives rise to an incompletely processed form of lamin a 1 2 9 progerin acts in a dominant gain of function fashion by accumulating at the nuclear periphery.

Stem cell lamin a. Induced pluripotent stem ips cells have been successfully generated from various types of cells and used to model human diseases. Lamin a c is expressed in embryonic stem cells. It has been shown that lamin a overexpression decreases both total yap levels and nuclear localization in mesenchymal stem cells. In mammals alternative splicing gives rise to lamin a and lamin c and the less abundant isoforms lamin aδ10 and lamin c2 fisher et al 1986.

Bone formation is a complex process regulated by chemical and mechanical cues coming from the surrounding extracellular matrix. In contrast increased yap nuclear localization and activity in combination with reduced lamin levels is observed in cancers of many organ types reviewed in 13 as well as in lmna mutant muscs cultured on soft. 1a escs were separated from the mef feeder cells see materials and methods and as expected expressed the pluripotency markers oct4 and nanog fig. Machiels et al 1996 a type lamins are absent in early embryonic cells but are present in.

This mutation activates a cryptic splice site and gives rise to a form of lamin a with a deletion of 50 amino acids near the c terminus. Lamins are grouped into a type and b type lamins. Combination of stem cell based approaches with gene editing technologies represents an attractive strategy for studying human disease and developing therapies. Progerin p02545 6 is a truncated version of the lamin a protein involved in the pathology of hutchinson gilford progeria syndrome progerin is most often generated by a single nucleotide polymorphism c1824t in the gene that codes for lamin a.

Lamin structure and assembly. Lamin a is an inner nuclear membrane protein that maintains nuclear structure integrity is involved in transcription dna damage response and genomic stability and also links to cell differentiation senescence premature aging and associated diseases. Furukawa et al 1994. In order to examine lamin expression levels we performed real time quantitative pcr on rna derived from escs neural progenitor cells npcs and mouse embryonic fibroblasts mefs fig.