Screening of Human cDNA Library Reveals Two differentiation-Related Genes, HHEX and HLX, as Promoters of Early Phase Reprogramming toward Pluripotency. (8th July 2016)

• Record Type: Journal Article
• Authors: Yamakawa, Tatsuya; Sato, Yoshiko; Matsumura, Yasuko; Kobayashi, Yukiko; Kawamura, Yoshifumi; Goshima, Naoki; Yamanaka, Shinya; Okita, Keisuke
• Is Part Of: Stem cells. Volume 34:Number 11(2016:Nov.)
• Page Start: 2661
• Page End: 2669
• Publication Date: 2016-07-08
• Subjects: Induced pluripotent stem cell -- Reprogramming -- Human cDNA library -- Screening -- HHEX -- HLX; Cloning -- Periodicals; Clone cells -- Periodicals; Stem cells -- Periodicals; Cell Differentiation -- Periodicals; Cell Division -- Periodicals; Clone Cells -- Periodicals; Hematopoietic Stem Cells -- Periodicals; Stem Cells -- Periodicals; 571.84
• DOI: 10.1002/stem.2436
• Languages: English
• ISSNs: 1066-5099

Abstract

Abstract: Gene screenings have identified a number of reprogramming factors that induce pluripotency from somatic cells. However, the screening methods have mostly considered only factors that maintain pluripotency in embryonic stem cells, ignoring a potentially long list of other contributing factors involved. To expand the search, we developed a new screening method that examined 2, 008 human genes in the generation of human induced pluripotent stem cells (iPSCs), including not only pluripotent genes but also differentiation-related genes that suppress pluripotency. We found the top 100 genes that increased reprogramming efficiency and discovered they contained many differentiation-related genes and homeobox genes. We selected two, HHEX and HLX, for further analysis. These genes enhanced the appearance of premature reprograming cells in the early phase of human iPSC induction, but had inhibitory effect on the late phase. In addition, when expressed in human iPSCs, HHEX and HLX interfered with the pluripotent state, indicating inverse effects on somatic reprograming and pluripotent maintenance. These results demonstrate that our screening is useful for identifying differentiation-related genes in somatic reprograming. Abstract : We used a new screening strategy that investigated the effects of genes from a human cDNA library on reprogramming and discovered two genes, HHEX and HLX, which may offer new understanding on the induction of pluripotency.