Single-cell analyses of X Chromosome inactivation dynamics and pluripotency during differentiation

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Fältnamn	Indikatorer	Metadata
000		03229naa a2200397 4500
001		oai:prod.swepub.kib.ki.se:134354323
003		SwePub
008		240701s2016 \| \|\|\|\|\|\|\|\|\|\|\|000 \|\|eng\|
024	7	a http://kipublications.ki.se/Default.aspx?queryparsed=id:1343543232 URI
024	7	a https://doi.org/10.1101/gr.201954.1152 DOI
040		a (SwePub)ki
041		a engb eng
042		9 SwePub
072	7	a ref2 swepub-contenttype
072	7	a art2 swepub-publicationtype
100	1	a Chen, G4 aut
245	1 0	a Single-cell analyses of X Chromosome inactivation dynamics and pluripotency during differentiation
264		c 2016-08-02
264	1	b Cold Spring Harbor Laboratory,c 2016
520		a Pluripotency, differentiation, and X Chromosome inactivation (XCI) are key aspects of embryonic development. However, the underlying relationship and mechanisms among these processes remain unclear. Here, we systematically dissected these features along developmental progression using mouse embryonic stem cells (mESCs) and single-cell RNA sequencing with allelic resolution. We found that mESCs grown in a ground state 2i condition displayed transcriptomic profiles diffused from preimplantation mouse embryonic cells, whereas EpiStem cells closely resembled the post-implantation epiblast. Sex-related gene expression varied greatly across distinct developmental states. We also identified novel markers that were highly enriched in each developmental state. Moreover, we revealed that several novel pathways, including PluriNetWork and Focal Adhesion, were responsible for the delayed progression of female EpiStem cells. Importantly, we “digitalized” XCI progression using allelic expression of active and inactive X Chromosomes and surprisingly found that XCI states exhibited profound variability in each developmental state, including the 2i condition. XCI progression was not tightly synchronized with loss of pluripotency and increase of differentiation at the single-cell level, although these processes were globally correlated. In addition, highly expressed genes, including core pluripotency factors, were in general biallelically expressed. Taken together, our study sheds light on the dynamics of XCI progression and the asynchronicity between pluripotency, differentiation, and XCI.
700	1	a Schell, JPu Karolinska Institutet4 aut
700	1	a Benitez, JAu Karolinska Institutet4 aut
700	1	a Petropoulos, Su Karolinska Institutet4 aut
700	1	a Yilmaz, M4 aut
700	1	a Reinius, Bu Karolinska Institutet4 aut
700	1	a Alekseenko, Zu Karolinska Institutet4 aut
700	1	a Shi, LM4 aut
700	1	a Hedlund, Eu Karolinska Institutet4 aut
700	1	a Lanner, Fu Karolinska Institutet4 aut
700	1	a Sandberg, Ru Karolinska Institutet4 aut
700	1	a Deng, QLu Karolinska Institutet4 aut
710	2	a Karolinska Institutet4 org
773	0	t Genome researchd : Cold Spring Harbor Laboratoryg 26:10, s. 1342-1354q 26:10<1342-1354x 1549-5469x 1088-9051
856	4	u http://genome.cshlp.org/content/26/10/1342.full.pdf
856	4 8	u http://kipublications.ki.se/Default.aspx?queryparsed=id:134354323
856	4 8	u https://doi.org/10.1101/gr.201954.115

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Av författaren/redakt...: Chen, G; Schell, JP; Benitez, JA; Petropoulos, S; Yilmaz, M; Reinius, B; visa fler...; Alekseenko, Z; Shi, LM; Hedlund, E; Lanner, F; Sandberg, R; Deng, QL; visa färre...

Artiklar i publikationen: Genome research

Av lärosätet: Karolinska Institutet

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