scholarly journals Visualizing Cell Cycle Phase Organization and Control During Neural Lineage Elaboration

Cells ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 2112
Author(s):  
Fatma Rabia Urun ◽  
Adrian W Moore
Keyword(s):  
Cell Cycle ◽  
Cell Fate ◽  
Cell Types ◽  
Cell Cycle Phase ◽  
Cycle Phase ◽  
Cell Cycle Regulators ◽  
Neural Lineage ◽  
Fate Control ◽  
A Cell ◽  
Cell Fate Control

In neural precursors, cell cycle regulators simultaneously control both progression through the cell cycle and the probability of a cell fate switch. Precursors act in lineages, where they transition through a series of cell types, each of which has a unique molecular identity and cellular behavior. Thus, investigating links between cell cycle and cell fate control requires simultaneous identification of precursor type and cell cycle phase, as well as an ability to read out additional regulatory factor expression or activity. We use a combined FUCCI-EdU labelling protocol to do this, and then apply it to the embryonic olfactory neural lineage, in which the spatial position of a cell correlates with its precursor identity. Using this integrated model, we find the CDKi p27KIP1 has different regulation relative to cell cycle phase in neural stem cells versus intermediate precursors. In addition, Hes1, which is the principle transcriptional driver of neural stem cell self-renewal, surprisingly does not regulate p27KIP1 in this cell type. Rather, Hes1 indirectly represses p27KIP1 levels in the intermediate precursor cells downstream in the lineage. Overall, the experimental model described here enables investigation of cell cycle and cell fate control linkage from a single precursor through to a lineage systems level.

scholarly journals Non-cell-autonomous promotion of pluripotency induction mediated by YAP

2018 ◽  
Author(s):  
Amaleah Hartman ◽  
Xiao Hu ◽  
Xinyue Chen ◽  
Anna E. Eastman ◽  
Cindy Yang ◽  
...  
Keyword(s):  
Cell Fate ◽  
Pluripotent Stem Cells ◽  
Cell Types ◽  
Matricellular Proteins ◽  
Fate Control ◽  
Promotional Effect ◽  
Cellular Context ◽  
Opposing Effects ◽  
Cell Fate Control ◽  
Heterologous Cell

SUMMARYWhile Yes-associated protein (YAP) antagonizes pluripotency during early embryogenesis, it has also been shown to promote stemness of multiple stem cell types, including pluripotent stem cells. Whether cellular context underlies these distinct functions of YAP in pluripotency remains unclear. Here, we establish that depending on the specific cells in which it is expressed, YAP exhibits opposing effects on pluripotency induction from somatic cells. Specifically, YAP inhibits pluripotency induction cell-autonomously but promotes it non-cell-autonomously. For its non-cell-autonomous role, YAP alters the expression of many secreted and matricellular proteins including CYR61, which recapitulates the promotional effect when added as a recombinant protein. Thus, we define a unique YAP-driven non-cell-autonomous process that enhances pluripotency induction. Our work highlights the importance of considering the distinct contributions from heterologous cell types in deciphering the mechanism of cell fate control and calls for careful re-examination of the co-existing bystander cells in complex cultures or tissues.

scholarly journals Heterogeneous Nuclear Ribonucleoprotein C Modulates Translation of c-myc mRNA in a Cell Cycle Phase-Dependent Manner

2003 ◽  
Vol 23 (2) ◽  
pp. 708-720 ◽  
Author(s):  
Jong Heon Kim ◽  
Ki Young Paek ◽  
Kobong Choi ◽  
Tae-Don Kim ◽  
Bumsuk Hahm ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Phase ◽  
In Vitro Translation ◽  
Cycle Phase ◽  
Dependent Manner ◽  
Heterogeneous Nuclear Ribonucleoprotein ◽  
M Phase ◽  
Hnrnp C ◽  
A Cell ◽  
Nuclear Ribonucleoprotein

ABSTRACT The c-myc proto-oncogene plays a key role in the proliferation, differentiation, apoptosis, and regulation of the cell cycle. Recently, it was demonstrated that the 5′ nontranslated region (5′ NTR) of human c-myc mRNA contains an internal ribosomal entry site (IRES). In this study, we investigated cellular proteins interacting with the IRES element of c-myc mRNA. Heterogeneous nuclear ribonucleoprotein C (hnRNP C) was identified as a cellular protein that interacts specifically with a heptameric U sequence in the c-myc IRES located between two alternative translation initiation codons CUG and AUG. Moreover, the addition of hnRNP C1 in an in vitro translation system enhanced translation of c-myc mRNA. Interestingly, hnRNP C was partially relocalized from the nucleus, where most of the hnRNP C resides at interphase, to the cytoplasm at the G2/M phase of the cell cycle. Coincidently, translation mediated through the c-myc IRES was increased at the G2/M phase when cap-dependent translation was partially inhibited. On the other hand, a mutant c-myc mRNA lacking the hnRNP C-binding site, showed a decreased level of translation at the G2/M phase compared to that of the wild-type message. Taken together, these findings suggest that hnRNP C, via IRES binding, modulates translation of c-myc mRNA in a cell cycle phase-dependent manner.

Dynamically-enhanced retention of gold nanoclusters in HeLa cells following X-rays exposure: A cell cycle phase-dependent targeting approach

2016 ◽  
Vol 119 (3) ◽  
pp. 544-551 ◽  
Author(s):  
Yan Liu ◽  
Weiqiang Chen ◽  
Pengcheng Zhang ◽  
Xiaodong Jin ◽  
Xinguo Liu ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Hela Cells ◽  
Gold Nanoclusters ◽  
Cell Cycle Phase ◽  
Cycle Phase ◽  
X Rays ◽  
A Cell

scholarly journals Characterizing and inferring quantitative cell cycle phase in single-cell RNA-seq data analysis

2019 ◽  
Author(s):  
Chiaowen Joyce Hsiao ◽  
PoYuan Tung ◽  
John D. Blischak ◽  
Jonathan E. Burnett ◽  
Kenneth A. Barr ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Cycle ◽  
Single Cell ◽  
Cell Cycle Progression ◽  
Cell Types ◽  
Cell Cycle Phase ◽  
Cellular Heterogeneity ◽  
Cycle Phase ◽  
Cycle Progression ◽  
Cellular Environment

AbstractCellular heterogeneity in gene expression is driven by cellular processes such as cell cycle and cell-type identity, and cellular environment such as spatial location. The cell cycle, in particular, is thought to be a key driver of cell-to-cell heterogeneity in gene expression, even in otherwise homogeneous cell populations. Recent advances in single-cell RNA-sequencing (scRNA-seq) facilitate detailed characterization of gene expression heterogeneity, and can thus shed new light on the processes driving heterogeneity. Here, we combined fluorescence imaging with scRNA-seq to measure cell cycle phase and gene expression levels in human induced pluripotent stem cells (iPSCs). Using these data, we developed a novel approach to characterize cell cycle progression. While standard methods assign cells to discrete cell cycle stages, our method goes beyond this, and quantifies cell cycle progression on a continuum. We found that, on average, scRNA-seq data from only five genes predicted a cell’s position on the cell cycle continuum to within 14% of the entire cycle, and that using more genes did not improve this accuracy. Our data and predictor of cell cycle phase can directly help future studies to account for cell-cycle-related heterogeneity in iPSCs. Our results and methods also provide a foundation for future work to characterize the effects of the cell cycle on expression heterogeneity in other cell types.

scholarly journals Yeast cell fate control by temporal redundancy modulation of transcription factor paralogs

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Yan Wu ◽  
Jiaqi Wu ◽  
Minghua Deng ◽  
Yihan Lin
Keyword(s):  
Transcription Factor ◽  
Transcription Factors ◽  
Stress Response ◽  
Cell Fate ◽  
Functional Redundancy ◽  
Yeast Cells ◽  
Fate Control ◽  
A Cell ◽  
Temporal Redundancy ◽  
Cell Fate Control

AbstractRecent single-cell studies have revealed that yeast stress response involves transcription factors that are activated in pulses. However, it remains unclear whether and how these dynamic transcription factors temporally interact to regulate stress survival. Here we show that budding yeast cells can exploit the temporal relationship between paralogous general stress regulators, Msn2 and Msn4, during stress response. We find that individual pulses of Msn2 and Msn4 are largely redundant, and cells can enhance the expression of their shared targets by increasing their temporal divergence. Thus, functional redundancy between these two paralogs is modulated in a dynamic manner to confer fitness advantages for yeast cells, which might feed back to promote the preservation of their redundancy. This evolutionary implication is supported by evidence from Msn2/Msn4 orthologs and analyses of other transcription factor paralogs. Together, we show a cell fate control mechanism through temporal redundancy modulation in yeast, which may represent an evolutionarily important strategy for maintaining functional redundancy between gene duplicates.

scholarly journals Dependence of cell-type proportioning and sorting on cell cycle phase in Dictyostelium discoideum

1984 ◽  
Vol 70 (1) ◽  
pp. 133-145 ◽  
Author(s):  
C.J. Weijer ◽  
G. Duschl ◽  
C.N. David
Keyword(s):  
Cell Cycle ◽  
Stationary Phase ◽  
Dictyostelium Discoideum ◽  
Cell Cycle Phase ◽  
Cycle Phase ◽  
Cell Type ◽  
Slime Mould ◽  
Synchronous Cell ◽  
A Cell ◽  
The Relationship

The relationship between the cell cycle phase of vegetative amoebae and prestalk and prespore differentiation in the slug stage were investigated in the slime mould Dictyostelium discoideum. Cells were synchronized by release from the stationary phase. Samples were taken at various times during the course of a synchronous cell doubling, fluorescently labelled and mixed with cells of random cell cycle phase from exponentially growing cultures. The fate of the fluorescently labelled cells was recorded at the slug stage. Cells early in the cycle exhibit strong prestalk sorting; cells taken later in the cycle exhibit strong prespore sorting. The period of prestalk sorting occurs immediately following mitosis and lasts about 1 h in a cell cycle of about 7 h duration. Accompanying the altered sorting behaviour is a marked changed in the prestalk-prespore proportions in slugs formed from synchronized populations of cells. Cells synchronized early in the cycle form slugs with 55% prespore cells; cells synchronized late in the cycle form slugs with 90% prespore. The results are discussed in terms of models for the formation of the prestalk-prespore pattern in slugs.

scholarly journals Constricted migration increases DNA damage and independently represses cell cycle

2018 ◽  
Vol 29 (16) ◽  
pp. 1948-1962 ◽  
Author(s):  
Charlotte R. Pfeifer ◽  
Yuntao Xia ◽  
Kuangzheng Zhu ◽  
Dazhen Liu ◽  
Jerome Irianto ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Dna Damage ◽  
Dna Repair ◽  
Cell Fate ◽  
Nuclear Lamina ◽  
Cell Cycle Phase ◽  
Cycle Phase ◽  
Cell Cycle Reentry ◽  
Γh2ax Foci ◽  
And Migration

Cell migration through dense tissues or small capillaries can elongate the nucleus and even damage it, and any impact on cell cycle has the potential to affect various processes including carcinogenesis. Here, nuclear rupture and DNA damage increase with constricted migration in different phases of cell cycle—which we show is partially repressed. We study several cancer lines that are contact inhibited or not and that exhibit diverse frequencies of nuclear lamina rupture after migration through small pores. DNA repair factors invariably mislocalize after migration, and an excess of DNA damage is evident as pan-­nucleoplasmic foci of phosphoactivated ATM and γH2AX. Foci counts are suppressed in late cell cycle as expected of mitotic checkpoints, and migration of contact-inhibited cells through large pores into sparse microenvironments leads also as expected to cell-cycle reentry and no effect on a basal level of damage foci. Constricting pores delay such reentry while excess foci occur independent of cell-cycle phase. Knockdown of repair factors increases DNA damage independent of cell cycle, consistent with effects of constricted migration. Because such migration causes DNA damage and impedes proliferation, it illustrates a cancer cell fate choice of “go or grow.”

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