Abstract：
:The recent success of derivation of mammalian haploid embryonic stem cells (haESCs) has provided a powerful tool for large-scale functional analysis of the mammalian genome. However, haESCs rapidly become diploidized after differentiation, posing challenges for genetic analysis. Here, we show that the spontaneous diploidization of haESCs happens in metaphase due to mitotic slippage. Diploidization can be suppressed by small-molecule-mediated inhibition of CDK1 and ROCK. Through ROCK inhibition, we can generate haploid somatic cells of all three germ layers from haESCs, including terminally differentiated neurons. Using piggyBac transposon-based insertional mutagenesis, we generated a haploid neural cell library harboring genome-wide mutations for genetic screening. As a proof of concept, we screened for Mn2+-mediated toxicity and identified the Park2 gene. Our findings expand the applications of mouse haploid cell technology to somatic cell types and may also shed light on the mechanisms of ploidy maintenance.
journal_name
Cell Repjournal_title
Cell reportsauthors
He ZQ,Xia BL,Wang YK,Li J,Feng GH,Zhang LL,Li YH,Wan HF,Li TD,Xu K,Yuan XW,Li YF,Zhang XX,Zhang Y,Wang L,Li W,Zhou Qdoi
10.1016/j.celrep.2017.07.081subject
Has Abstractpub_date
2017-08-29 00:00:00pages
2227-2237issue
9issn
2211-1247pii
S2211-1247(17)31101-4journal_volume
20pub_type
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