scholarly journals Musashi1 Cooperates in Abnormal Cell Lineage Protein 28 (Lin28)-mediated Let-7 Family MicroRNA Biogenesis in Early Neural Differentiation

2011 ◽  
Vol 286 (18) ◽  
pp. 16121-16130 ◽  
Author(s):  
Hironori Kawahara ◽  
Yohei Okada ◽  
Takao Imai ◽  
Akio Iwanami ◽  
Paul S. Mischel ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Neural Differentiation ◽  
Rna Binding ◽  
Binding Protein ◽  
Embryonic Stem ◽  
Cell Lineage ◽  
Mirna Biogenesis ◽  
Neural Stem Progenitor Cells ◽  
Stem Cell Pluripotency

Musashi1 (Msi1) is an RNA-binding protein that is highly expressed in neural stem/progenitor cells (NS/PCs) as well as in other tissue stem cells. Msi1 binds to the 3′-UTR of its target mRNAs in NS/PCs, prevents their translation, and interferes with NS/PC differentiation. We previously showed that Msi1 competes with eIF4G to bind poly(A)-binding protein and inhibits assembly of the 80 S ribosome. Here we show that Msi1 works in concert with Lin28 to regulate post-transcriptional microRNA (miRNA) biogenesis in the cropping step, which occurs in the nucleus. Lin28 and its binding partner terminal uridylyltransferase 4 (TUT4) are known to maintain embryonic stem cell pluripotency by blocking let-7 miRNA biogenesis at the dicing step. Interestingly, we found that during early neural differentiation of embryonic stem cells, Msi1 enhanced the localization of Lin28 to the nucleus and also inhibited the nuclear cropping step of another let-7 family miRNA, miR98. These results suggest that Msi1 can influence stem cell maintenance and differentiation by controlling the subcellular localization of proteins involved in miRNA biogenesis, as well as by regulating the translation of its target mRNA.

scholarly journals Interplay of Oct4 with Sox2 and Sox17: a molecular switch from stem cell pluripotency to specifying a cardiac fate

2009 ◽  
Vol 186 (5) ◽  
pp. 665-673 ◽  
Author(s):  
Sonia Stefanovic ◽  
Nesrine Abboud ◽  
Stéphanie Désilets ◽  
David Nury ◽  
Chad Cowan ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Embryonic Stem ◽  
Cell Lineage ◽  
Dual Function ◽  
Cardiac Progenitors ◽  
Dual Action ◽  
Stem Cell Pluripotency ◽  
Induced Pluripotent ◽  
Dose Dependent

Oct4 exerts a dose-dependent dual action, as both a gatekeeper for stem cell pluripotency and in driving cells toward specific lineages. Here, we identify the molecular mechanism underlying this dual function. BMP2- or transgene-induced Oct4 up-regulation drives human embryonic and induced pluripotent stem cells to become cardiac progenitors. When embryonic stem cell pluripotency is achieved, Oct4 switches from the Sox2 to the Sox17 promoter. This switch allows the cells to turn off the pluripotency Oct4-Sox2 loop and to turn on the Sox17 promoter. This powerful process generates a subset of endoderm-expressing Sox17 and Hex, both regulators of paracrine signals for cardiogenesis (i.e., Wnt, BMP2) released into the medium surrounding colonies of embryonic stem cells. Our data thus reveal a novel molecular Oct4- and Sox17-mediated mechanism that disrupts the stem cell microenvironment favoring pluripotency to provide a novel paracrine endodermal environment in which cell lineage is determined and commits the cells to a cardiogenic fate.

scholarly journals Uncovering the RNA-binding protein landscape in the pluripotency network of human embryonic stem cells

Cell Reports ◽  
2021 ◽  
Vol 35 (9) ◽  
pp. 109198
Author(s):  
Shlomi Dvir ◽  
Amir Argoetti ◽  
Chen Lesnik ◽  
Mark Roytblat ◽  
Kohava Shriki ◽  
...  
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Human Embryonic Stem Cells ◽  
Rna Binding ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
Embryonic Stem

scholarly journals Lineage specification of early embryos and embryonic stem cells at the dawn of enabling technologies

2017 ◽  
Vol 4 (4) ◽  
pp. 533-542 ◽  
Author(s):  
Guangdun Peng ◽  
Patrick P. L. Tam ◽  
Naihe Jing
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cell Biology ◽  
Developmental Process ◽  
Embryonic Stem ◽  
Molecular Signaling ◽  
Lineage Specification ◽  
Genomic Technologies ◽  
Enabling Technologies ◽  
Stem Cell Pluripotency

Abstract Establishment of progenitor cell populations and lineage diversity during embryogenesis and the differentiation of pluripotent stem cells is a fascinating and intricate biological process. Conceptually, an understanding of this developmental process provides a framework to integrate stem-cell pluripotency, cell competence and differentiating potential with the activity of extrinsic and intrinsic molecular determinants. The recent advent of enabling technologies of high-resolution transcriptome analysis at the cellular, population and spatial levels proffers the capability of gaining deeper insights into the attributes of the gene regulatory network and molecular signaling in lineage specification and differentiation. In this review, we provide a snapshot of the emerging enabling genomic technologies that contribute to the study of development and stem-cell biology.

scholarly journals Epsins Regulate Mouse Embryonic Stem Cell Exit from Pluripotency and Neural Commitment by Controlling Notch Activation

2019 ◽  
Vol 2019 ◽  
pp. 1-13 ◽  
Author(s):  
Marina Cardano ◽  
Jacopo Zasso ◽  
Luca Ruggiero ◽  
Giuseppina Di Giacomo ◽  
Matteo Marcatili ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Embryonic Stem Cells ◽  
Notch Signaling ◽  
Neural Differentiation ◽  
Radial Glia ◽  
Embryonic Stem ◽  
Mouse Embryonic Stem Cell ◽  
Neural Progenitors ◽  
Notch Activation

Epsins are part of the internalization machinery pivotal to control clathrin-mediated endocytosis. Here, we report that epsin family members are expressed in mouse embryonic stem cells (mESCs) and that epsin1/2 knockdown alters both mESC exits from pluripotency and their differentiation. Furthermore, we show that epsin1/2 knockdown compromises the correct polarization and division of mESC-derived neural progenitors and their conversion into expandable radial glia-like neural stem cells. Finally, we provide evidence that Notch signaling is impaired following epsin1/2 knockdown and that experimental restoration of Notch signaling rescues the epsin-mediated phenotypes. We conclude that epsins contribute to control mESC exit from pluripotency and allow their neural differentiation by appropriate modulation of Notch signaling.

scholarly journals Maintenance of active chromatin states by Hmgn1 and Hmgn2 is required for stem cell identity:

2018 ◽  
Author(s):  
Sylvia Garza-Manero ◽  
Abdulmajeed A. A. Sindi ◽  
Gokula Mohan ◽  
Ohoud Rehbini ◽  
Valentine H. M. Jeantet ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Neuronal Differentiation ◽  
Embryonic Stem ◽  
Adult Brain ◽  
Active Chromatin ◽  
Cell Identity ◽  
Chromatin States ◽  
Neural Stem Progenitor Cells ◽  
Chromatin Configuration

Chromatin plasticity is thought to be fundamental to the pluripotency of embryonic stem cells. Hmgn proteins modulate chromatin structure and are highly expressed during early development and in neural stem/progenitor cells of the developing and adult brain. Here, we show that loss of Hmgn1 or Hmgn2 in pluripotent embryonal carcinoma cells leads to increased levels of spontaneous neuronal differentiation. This is accompanied by the loss of pluripotency markers and increased expression of the pro-neural transcription factors Neurog1 and Ascl1. Neural stem cells derived from these Hmgn-knockout lines also show increased spontaneous neuronal differentiation and Neurog1 expression. The loss of Hmgn2 is associated with the disruption of active chromatin states at specific classes of gene. The levels of H3K4me3, H3K9ac, H3K27ac and H3K122ac are considerably reduced at the pluripotency genes Nanog and Oct4, which impacts transcription. At endodermal/mesodermal lineage-specific genes, the loss of Hmgn2 leads to a switch from a bivalent to a repressive chromatin configuration. However, at the neuronal lineage genes Neurog1 and Ascl1, no epigenetic changes are observed and their bivalent states are retained. We conclude that Hmgn proteins play important roles in maintaining chromatin plasticity in stem cells, and are essential for maintaining stem cell identity and pluripotency.

Lox2, a putative leech segment identity gene, is expressed in the same segmental domain in different stem cell lineages

Development ◽  
1992 ◽  
Vol 116 (3) ◽  
pp. 697-710 ◽  
Author(s):  
D. Nardelli-Haefliger ◽  
M. Shankland
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Embryonic Stem ◽  
Cell Lineage ◽  
Gene Products ◽  
Cell Lineages ◽  
Stem Cell Lineage ◽  
Hybridization Reaction ◽  
Cell Segment

The segmented tissues of the adult leech arise from a set of five, bilaterally paired embryonic stem cells via a stereotyped sequence of cell lineage. Individual segments exhibit unique patterns of cell differentiation, and previous studies have suggested that each stem cell lineage establishes at least some aspects of its own segmental specificity autonomously. In this paper, we describe a putative leech segment identity gene, Lox2, and examine its expression in the various stem cell lineages. Both sequence analysis and the segmental pattern of Lox2 expression suggest a specific homology to the fruitfly segment identity genes Ubx and abdA. In situ hybridization reveals a cellular accumulation of Lox2 RNA over a contiguous domain of 16 midbody segments (M6-M21), including postmitotic neurons, muscles and the differentiating genitalia. Lox2 transcripts were not detected at the stage when segment identities are first established, suggesting that Lox2 gene products may not be part of the initial specification process. Individual stem cell lineages were labeled by intracellular injection of fluorescent tracers, and single cell colocalization of lineage tracer and hybridization reaction product revealed expression of Lox2 RNA in the progeny of four different stem cells. The segmental domain of Lox2 RNA was very similar in the various stem cell lineages, despite the fact that some stem cells generate one founder cell/segment, whereas other stem cells generate two founder cells/segment.

scholarly journals Cold-Inducible RNA-Binding Protein Bypasses Replicative Senescence in Primary Cells through Extracellular Signal-Regulated Kinase 1 and 2 Activation

2009 ◽  
Vol 29 (7) ◽  
pp. 1855-1868 ◽  
Author(s):  
Ana Artero-Castro ◽  
Francisco B. Callejas ◽  
Josep Castellvi ◽  
Hiroshi Kondoh ◽  
Amancio Carnero ◽  
...  
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Rna Binding ◽  
Replicative Senescence ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
Embryonic Stem ◽  
Primary Cells ◽  
Extracellular Signal Regulated Kinase ◽  
Extracellular Signal

ABSTRACT Embryonic stem cells are immortalized cells whose proliferation rate is comparable to that of carcinogenic cells. To study the expression of embryonic stem cell genes in primary cells, genetic screening was performed by infecting mouse embryonic fibroblasts (MEFs) with a cDNA library from embryonic stem cells. Cold-inducible RNA-binding protein (CIRP) was identified due to its ability to bypass replicative senescence in primary cells. CIRP enhanced extracellular signal-regulated kinase 1 and 2 (ERK1/2) phosphorylation, and treatment with an MEK inhibitor decreased the proliferation caused by CIRP. In contrast to CIRP upregulation, CIRP downregulation decreased cell proliferation and resulted in inhibition of phosphorylated ERK1/2 inhibition. This is the first evidence that ERK1/2 activation, through the same mechanism as that described for a Val12 mutant K-ras to induce premature senescence, is able to bypass senescence in the absence of p16INK4a, p21WAF1, and p19ARF upregulation. Moreover, these results show that CIRP functions by stimulating general protein synthesis with the involvement of the S6 and 4E-BP1 proteins. The overall effect is an increase in kinase activity of the cyclin D1-CDK4 complex, which is in accordance with the proliferative capacity of CIRP MEFs. Interestingly, CIRP mRNA and protein were upregulated in a subgroup of cancer patients, a finding that may be of relevance for cancer research.

Neural differentiation of mouse embryonic stem cells

2003 ◽  
Vol 31 (1) ◽  
pp. 45-49 ◽  
Author(s):  
M.P. Stavridis ◽  
A.G. Smith
Keyword(s):  
Stem Cells ◽  
Central Nervous System ◽  
Nervous System ◽  
Stem Cell ◽  
Embryonic Stem Cells ◽  
Neural Differentiation ◽  
Embryonic Stem ◽  
Cell Replacement ◽  
Quantification Analysis ◽  
The Central Nervous System

Pluripotent embryonic stem cells can give rise to neuroectodermal derivatives in culture. This potential could be harnessed to generate neurons and glia for cell-replacement therapies in the central nervous system and for use in drug discovery. However, current methods of neural differentiation are empirical and relatively innefficient. Here, we review these methodologies and present new tools for quantification, analysis and manipulation of embryonic stem cell neural determination.

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