Dynamics extracted from fixed cells reveal feedback linking cell growth to cell cycle

Kafri, Ran; Levy, Jason; Ginzberg, Miriam Bracha; Oh, Seungeun; Lahav, Galit; Kirschner, Marc W.

doi:10.1038/nature11897

Cited by 228 publications

(331 citation statements)

References 10 publications

(11 reference statements)

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“…Regarding the cell size shown in Figure 10c, treatment with aphidicolin made erythrocytes larger in each stage, indicating that S-phase arrest made erythrocytes larger, which confirms the occurrence of S-phase arrest of erythrocytes in kyo at phase 2, consistent with previous studies that show the importance of Sphase in the growth of cells (Dolznig et al, 2004;Kafri et al, 2013). In the treatment with colchicine at st30 and sampling at st31, the cell/nucleus size did not change, though erythrocytes treated with control DMSO were temporarily miniaturized indicating that the temporary miniaturization of cells/nuclei in erythrocytes at st30 was coordinated with cell division in the blood flow.…”

Section: Cell-cycle Inhibitors Conducted Erythrocytes Larger or Prevesupporting

confidence: 90%

Proliferation following tetraploidization regulates the size and number of erythrocytes in the blood flow during medaka development, as revealed by the abnormal karyotype of erythrocytes in the medaka TFDP1 mutant

Taimatsu

Takubo

Maruyama³

et al. 2015

Developmental Dynamics

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Background: For the delivery of oxygen, the correct size/number of erythrocytes is required for proper blood flow. Results: By combined analyses of wild-type (WT) medaka and the kyoho (kyo) mutant, we found proliferation-mediated adaptation for size/number of erythrocytes in the blood flow during medaka development. Before the start of heart beating in the WT medaka, the karyotype of erythrocytes was 2N-4N. After the start of blood flow, the karyotype changed to 4N-8N with tetraploidization, and the cell size became larger. After the start of intersegmental and pharyngeal blood flow, the erythrocytes became smaller. The medaka mutant kyo showed erythrocytes of large size, and positional cloning of kyo demonstrated the candidate gene TFDP1, indicating higher polyploidization due to arrest in S-phase in erythrocytes of the kyo mutant. Conclusions: From our findings, we uncovered a previously unrecognized system for the regulation of the size/number in the blood flow:proliferation of erythrocytes following tetraploidization during embryonic development. Developmental Dynamics 244:651-668, 2015. IntroductionBlood flow carries oxygen to the whole body, and impact to blood circulation whether by mechanical obstruction in the case of polycythemia or thrombocytosis or by functional abnormalities such as anemia may cause serious health concerns (Demirog lu, 1997;Tefferi, 2003;Weiss and Goodnough, 2005). Because of the closed system of blood circulation, blood flow requires the correct size/number of erythrocytes (Tamplin and Zon, 2010;Sankaran et al., 2012). Active angiogenesis during embryonic development introduces intricate blood flow and burdens erythrocytes with two tasks: having the proper size and number for maintenance of blood flow. As to the number, longer blood vessels require more erythrocytes; however, too many erythrocytes block the blood flow (Tefferi, 2003). Regarding size, narrower blood vessels require smaller erythrocytes; however, small erythrocytes cannot carry enough oxygen. Thus, erythrocytes are required to have adaptability to afford an adequate size/number due to the change of blood flow. In a previous study, the start of blood circulation was shown to affect angiogenesis (Udan et al., 2013), but relationships between the length and diameter of blood vessels and the size/number of erythrocytes during development have remained unclear, because mice are not suitable for such studies. Therefore, we decided to use the medaka fish as a model animal to observe blood flow in early developmental stages. Compared to mice, medaka have a transparent body and quick development, both of which are beneficial for observing erythrocytes in the change of blood flow throughout the whole developmental process (Wittbrodt et al., 2002). The question arises as to how embryonic erythrocytes regulate their size/number to adapt to the change of blood flow during medaka development. In this study, we divided the blood flow event into 3 phases during medaka development to study the relationship between angiogenesis and t...

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Section: Cell-cycle Inhibitors Conducted Erythrocytes Larger or Prevesupporting

confidence: 90%

Proliferation following tetraploidization regulates the size and number of erythrocytes in the blood flow during medaka development, as revealed by the abnormal karyotype of erythrocytes in the medaka TFDP1 mutant

Taimatsu

Takubo

Maruyama³

et al. 2015

Developmental Dynamics

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“…The parameters examined, including cell size, [31][32][33] have been observed to be associated with cell growth and we looked at cell number after culture ( Figure 13). Cultures on (-) pMA imprint had a larger population of cells than those on (f)pMA.…”

Section: Cell Numbermentioning

confidence: 99%

The characteristics of Ishikawa endometrial cancer cells are modified by substrate topography with cell-like features and the polymer surface

Tan

Sykes

Alkaisi

et al. 2015

IJN

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Conventional in vitro culture studies on flat surfaces do not reproduce tissue environments, which have inherent topographical mechanical signals. To understand the impact of these mechanical signals better, we use a cell imprinting technique to replicate cell features onto hard polymer culture surfaces as an alternative platform for investigating biomechanical effects on cells; the high-resolution replication of cells offers the micro- and nanotopography experienced in typical cell–cell interactions. We call this platform a Bioimprint. Cells of an endometrial adenocarcinoma cell line, Ishikawa, were cultured on a bioimprinted substrate, in which Ishikawa cells were replicated on polymethacrylate (pMA) and polystyrene (pST), and compared to cells cultured on flat surfaces. Characteristics of cells, incorporating morphology and cell responses, including expression of adhesion-associated molecules and cell proliferation, were studied. In this project, we fabricated two different topographies for the cells to grow on: a negative imprint that creates cell-shaped hollows and a positive imprint that recreates the raised surface topography of a cell layer. We used two different substrate materials, pMA and pST. We observed that cells on imprinted substrates of both polymers, compared to cells on flat surfaces, exhibited higher expression of β1-integrin, focal adhesion kinase, and cytokeratin-18. Compared to cells on flat surfaces, cells were larger on imprinted pMA and more in number, whereas on pST-imprinted surfaces, cells were smaller and fewer than those on a flat pST surface. This method, which provided substrates in vitro with cell-like features, enabled the study of effects of topographies that are similar to those experienced by cells in vivo. The observations establish that such a physical environment has an effect on cancer cell behavior independent of the characteristics of the substrate. The results support the concept that the physical topography of a cell’s environment may modulate crucial oncological signaling pathways; this suggests the possibility of cancer therapies that target pathways associated with the response to mechanical stimuli.

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“…Recently, however, measurements of growth in human cell lines using microfluidic devices or on fixed steady-state populations with help of mathematical modeling, revealed regulatory events at the G 1 /S transition, decreasing cell size variation. [3][4][5] In the fission yeast Schizosaccharomyces pombe, a rod-shaped single-cell eukaryote that exhibits stereotyped patterns of growth by cell tip extension and division by medial cleavage, direct evidence for cell size control has existed since the 1970s, when it was shown that cells rapidly re-establish their normal length upon recovery from a transient cell cycle block. 6 In this organism, one major homeostatic mechanism operates at the G 2 /M transition, when cells can adjust the time spent in G 2 to divide only when a specific cell size has been reached.…”

Section: Introductionmentioning

confidence: 99%

Distinct levels in Pom1 gradients limit Cdr2 activity and localization to time and position division

et al. 2013

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Dynamics extracted from fixed cells reveal feedback linking cell growth to cell cycle

Cited by 228 publications

References 10 publications

Proliferation following tetraploidization regulates the size and number of erythrocytes in the blood flow during medaka development, as revealed by the abnormal karyotype of erythrocytes in the medaka TFDP1 mutant

Proliferation following tetraploidization regulates the size and number of erythrocytes in the blood flow during medaka development, as revealed by the abnormal karyotype of erythrocytes in the medaka TFDP1 mutant

The characteristics of Ishikawa endometrial cancer cells are modified by substrate topography with cell-like features and the polymer surface

Distinct levels in Pom1 gradients limit Cdr2 activity and localization to time and position division

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