Molecular signature of human embryonic stem cells and its comparison with the mouse

Satô, Noboru; Sanjuan, Ignacio Munoz; Heke, Michael; Uchida, Makiko; Naef, Félix; Brivanlou, Ali H.

doi:10.1016/s0012-1606(03)00256-2

Cited by 430 publications

(399 citation statements)

References 36 publications

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“…Most obviously, they need different culture conditions and exhibit significant difference in colony morphology, growth rate, surface markers, and differentiation potential. Their differences were further demonstrated by the global molecular signatures (Sato et al, 2003;Rao, 2004) and the signaling pathways (Okita and Yamanaka, 2006) that regulating self-renewal and differentiation. Whether the dissimilarity between these two type of ESCs is because of the intrinsic difference between species or simply due to an unmatchable developmental stages of these two types of PSCs (Rossant, 2008) have become a critical question of human stem cell biology.…”

Section: Revisiting the Pluripotency Of Hescsmentioning

confidence: 99%

Specification of functional neurons and glia from human pluripotent stem cells

Jiang

Zhang

2012

Protein Cell

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Human pluripotent stem cells (PSCs) such as embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) hold great promise in regenerative medicine as they are an important source of functional cells for potential cell replacement. These human PSCs, similar to their counterparts of mouse, have the full potential to give rise to any type of cells in the body. However, for the promise to be fulfilled, it is necessary to convert these PSCs into functional specialized cells. Using the developmental principles of neural lineage specification, human ESCs and iPSCs have been effectively differentiated to regional and functional specific neurons and glia, such as striatal gama-aminobutyric acid (GABA)-ergic neurons, spinal motor neurons and myelin sheath forming oligodendrocytes. The human PSCs, in general differentiate after the similar developmental program as that of the mouse: they use the same set of cell signaling to tune the cell fate and they share a conserved transcriptional program that directs the cell fate transition. However, the human PSCs, unlike their counterparts of mouse, tend to respond divergently to the same set of extracellular signals at certain stages of differentiation, which will be a critical consideration to translate the animal model based studies to clinical application.

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Section: Revisiting the Pluripotency Of Hescsmentioning

confidence: 99%

Specification of functional neurons and glia from human pluripotent stem cells

Jiang

Zhang

2012

Protein Cell

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“…A large dataset on gene expression of undifferentiated hESCs and EBs that differentiated from them has been generated using large-scale array experiments, including MPSS, EST enumeration, and microarrays, and described by a variety of investigators [17][18][19][20][21][22][23][24]. To generate a list of genes characteristic of undifferentiated hESCs and differentiated EBs, we examined three published reports on gene expression in hESCs and EBs: (a) a list of 92 genes identified as "stemness" genes that are expressed at high levels in six hESC lines as assessed by a 16,695 70-bp oligonucleotide microarray [18], (b) a comprehensive list of genes common to undifferentiated hESCs obtained by MPSS analysis using pooled hESCs samples [17], and (c) a large list of genes that are highly expressed in differentiated EBs detected by both MPSS and EST scan [19].…”

Section: Meta-analysis Proceduresmentioning

confidence: 99%

“…hESCs are also similar in their ability to proliferate and differentiate into cell types of the three germ layers in vitro and in vivo [9 -16]. Properties of hESCs have also been compared using microarray, expressed sequence tag (EST) scan, serial analysis of gene expression (SAGE), and massively parallel signature sequencing (MPSS) [4,[17][18][19][20][21][22][23][24][25][26][27]. These studies suggest that it is likely that markers shared by hESC lines, but absent in other cell populations, exist.…”

Section: Introductionmentioning

confidence: 99%

Assessing Self-Renewal and Differentiation in Human Embryonic Stem Cell Lines

et al. 2005

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Like other cell populations, undifferentiated human embryonic stem cells (hESCs) express a characteristic set of proteins and mRNA that is unique to the cells regardless of culture conditions, number of passages, and methods of propagation. We sought to identify a small set of markers that would serve as a reliable indicator of the balance of undifferentiated and differentiated cells in hESC populations. Markers of undifferentiated cells should be rapidly downregulated as the cells differentiate to form embryoid bodies (EBs), whereas markers that are absent or low during the undifferentiated state but that are induced as hESCs differentiate could be used to assess the presence of differentiated cells in the cultures. In this paper, we describe a list of markers that reliably distinguish undifferentiated and differentiated cells. An initial list of approximately 150 genes was generated by scanning published massively parallel signature sequencing, expressed sequence tag scan, and microarray datasets. From this list, a subset of 109 genes was selected that included 55 candidate markers of undifferentiated cells, 46 markers of hESC derivatives, four germ cell markers, and four trophoblast markers. Expression of these candidate marker genes was analyzed in undifferentiated hESCs and differentiating EB populations in four different lines by immunocytochemistry, reverse transcription-polymerase chain reaction (RT-PCR), microarray analysis, and quantitative RT-PCR (qPCR). We show that qPCR, with as few as 12 selected genes, can reliably distinguish differentiated cells from undifferentiated hESC populations.

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“…The unique proliferative properties of human ES cells may be related to a naïve transcriptome which is dedicated to self-propagation through mitotic cell division and sustenance of a pluripotent uncommitted state (Thomson et al, 1998;Amit et al, 2000;Pera et al, 2000;Bhattacharya et al, 2004;Brandenberger et al, 2004;Miura et al, 2004;Rao et al, 2004;Boyer et al, 2005;Wei et al, 2005). Defining the molecular basis of pluripotency and the capability of human ES cells for self renewal is critical for the rational design of biomedical applications of human ES cells as a cellular source for tissue replacement (Carpenter et al, 2003;Sato et al, 2003;Heins et al, 2004;Stojkovic et al, 2004;Zwaka and Thomson, 2005).…”

mentioning

confidence: 99%

Cell cycle dependent phosphorylation and subnuclear organization of the histone gene regulator p220^NPAT in human embryonic stem cells

Ghule

Becker

Harper

et al. 2007

Journal Cellular Physiology

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Human embryonic stem (ES) cells have an expedited cell cycle ($15 h) due to an abbreviated G1 phase ($2.5 h) relative to somatic cells. One principal regulatory event during cell cycle progression is the G1/S phase induction of histone biosynthesis to package newly replicated DNA. In somatic cells, histone H4 gene expression is controlled by CDK2 phosphorylation of p220 NPAT and localization of HiNF-P/p220 NPAT complexes with histone genes at Cajal body related subnuclear foci. Here we show that this 'S point' pathway is operative in situ in human ES cells (H9 cells; NIH-designated WA09). Immunofluorescence microscopy shows an increase in p220 NPAT foci in G1 reflecting the assembly of histone gene regulatory complexes in situ. In contrast to somatic cells where duplication of p220 NPAT foci is evident in S phase, the increase in the number of p220 NPAT foci in ES cells appears to precede the onset of DNA synthesis as measured by BrdU incorporation. Phosphorylation of p220 NPAT at CDK dependent epitopes is most pronounced in S phase when cells exhibit elevated levels of cyclins E and A. Our data indicate that subnuclear organization of the HiNF-P/p220 NPAT pathway is rapidly established as ES cells emerge from mitosis and that p220 NPAT is subsequently phosphorylated in situ. Our findings establish that the HiNF-P/p220 NPAT gene regulatory pathway operates in a cell cycle dependent microenvironment that supports expression of DNA replication-linked histone genes and chromatin assembly to accommodate human stem cell self-renewal.

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Molecular signature of human embryonic stem cells and its comparison with the mouse

Cited by 430 publications

References 36 publications

Specification of functional neurons and glia from human pluripotent stem cells

Specification of functional neurons and glia from human pluripotent stem cells

Assessing Self-Renewal and Differentiation in Human Embryonic Stem Cell Lines

Cell cycle dependent phosphorylation and subnuclear organization of the histone gene regulator p220^NPAT in human embryonic stem cells

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Molecular signature of human embryonic stem cells and its comparison with the mouse

Cited by 430 publications

References 36 publications

Specification of functional neurons and glia from human pluripotent stem cells

Specification of functional neurons and glia from human pluripotent stem cells

Assessing Self-Renewal and Differentiation in Human Embryonic Stem Cell Lines

Cell cycle dependent phosphorylation and subnuclear organization of the histone gene regulator p220NPAT in human embryonic stem cells

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Product

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Cell cycle dependent phosphorylation and subnuclear organization of the histone gene regulator p220^NPAT in human embryonic stem cells