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Dive into the research topics where Yitzhak Reizel is active.

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Featured researches published by Yitzhak Reizel.


Molecular Endocrinology | 2010

Sustained activity of the EGF receptor is an absolute requisite for LH-induced oocyte maturation and cumulus expansion.

Yitzhak Reizel; Judith Elbaz; Nava Dekel

Mammalian reproduction depends on the release of a mature oocyte from the ovarian follicle. Maturation of the oocyte and rupture of the follicle wall constitute part of the responses to the preovulatory surge of LH, which also include cumulus expansion and granulosa cell luteinization. It was previously shown that the epidermal growth factor receptor (EGFR) mediates the ovulatory response to LH in the ovarian follicle. We hypothesized that it is a sustained activity of the EGFR that generates oocyte maturation and cumulus expansion. We demonstrated that, whereas a transient exposure of rat isolated, intact, preovulatory follicles to either LH or forskolin was sufficient to induce oocyte maturation and cumulus expansion, these LH-induced responses were only generated upon a prolonged activity of the EGFR. In addition, the continuous activity of the EGFR is essential for the chronic phosphorylation of the ERK1/2 downstream signaling molecules, which were shown to be essential for oocyte maturation and cumulus expansion. Interestingly, EGFR-sustained activity was also necessary to maintain the up-regulation of Ptgs2, a gene essential for cumulus expansion. The unusual prolonged duration of ERK1/2 activity may possibly be attributed to the late induction of the ERK-specific phosphatase 3, demonstrated herein. These new data shed light on the unique characteristics of EGFR-ERK1/2 activity in the ovarian follicle and emphasize the fact that the ovulatory process involves a nonclassical activation of this pathway.


PLOS Genetics | 2012

Cell Lineage Analysis of the Mammalian Female Germline

Yitzhak Reizel; Shalev Itzkovitz; Rivka Adar; Judith Elbaz; Adrian Jinich; Noa Chapal-Ilani; Yosef E. Maruvka; Nava Nevo; Zipora Marx; Inna Horovitz; Adam Wasserstrom; Avi Mayo; Irena Shur; Dafna Benayahu; Karl Skorecki; Eran Segal; Nava Dekel; Ehud Shapiro

Fundamental aspects of embryonic and post-natal development, including maintenance of the mammalian female germline, are largely unknown. Here we employ a retrospective, phylogenetic-based method for reconstructing cell lineage trees utilizing somatic mutations accumulated in microsatellites, to study female germline dynamics in mice. Reconstructed cell lineage trees can be used to estimate lineage relationships between different cell types, as well as cell depth (number of cell divisions since the zygote). We show that, in the reconstructed mouse cell lineage trees, oocytes form clusters that are separate from hematopoietic and mesenchymal stem cells, both in young and old mice, indicating that these populations belong to distinct lineages. Furthermore, while cumulus cells sampled from different ovarian follicles are distinctly clustered on the reconstructed trees, oocytes from the left and right ovaries are not, suggesting a mixing of their progenitor pools. We also observed an increase in oocyte depth with mouse age, which can be explained either by depth-guided selection of oocytes for ovulation or by post-natal renewal. Overall, our study sheds light on substantial novel aspects of female germline preservation and development.


PLOS Genetics | 2011

Colon Stem Cell and Crypt Dynamics Exposed by Cell Lineage Reconstruction

Yitzhak Reizel; Noa Chapal-Ilani; Rivka Adar; Shalev Itzkovitz; Judith Elbaz; Yosef E. Maruvka; Elad Segev; Liran I. Shlush; Nava Dekel; Ehud Y. Shapiro

Stem cell dynamics in vivo are often being studied by lineage tracing methods. Our laboratory has previously developed a retrospective method for reconstructing cell lineage trees from somatic mutations accumulated in microsatellites. This method was applied here to explore different aspects of stem cell dynamics in the mouse colon without the use of stem cell markers. We first demonstrated the reliability of our method for the study of stem cells by confirming previously established facts, and then we addressed open questions. Our findings confirmed that colon crypts are monoclonal and that, throughout adulthood, the process of monoclonal conversion plays a major role in the maintenance of crypts. The absence of immortal strand mechanism in crypts stem cells was validated by the age-dependent accumulation of microsatellite mutations. In addition, we confirmed the positive correlation between physical and lineage proximity of crypts, by showing that the colon is separated into small domains that share a common ancestor. We gained new data demonstrating that colon epithelium is clustered separately from hematopoietic and other cell types, indicating that the colon is constituted of few progenitors and ruling out significant renewal of colonic epithelium from hematopoietic cells during adulthood. Overall, our study demonstrates the reliability of cell lineage reconstruction for the study of stem cell dynamics, and it further addresses open questions in colon stem cells. In addition, this method can be applied to study stem cell dynamics in other systems.


PLOS Computational Biology | 2008

Estimating cell depth from somatic mutations.

Adam Wasserstrom; Dan Frumkin; Rivka Adar; Shalev Itzkovitz; Tomer Stern; Shai Kaplan; Gabi Shefer; Irena Shur; Lior Zangi; Yitzhak Reizel; Alon Harmelin; Yuval Dor; Nava Dekel; Yair Reisner; Dafna Benayahu; Eldad Tzahor; Eran Segal; Ehud Y. Shapiro

The depth of a cell of a multicellular organism is the number of cell divisions it underwent since the zygote, and knowing this basic cell property would help address fundamental problems in several areas of biology. At present, the depths of the vast majority of human and mouse cell types are unknown. Here, we show a method for estimating the depth of a cell by analyzing somatic mutations in its microsatellites, and provide to our knowledge for the first time reliable depth estimates for several cells types in mice. According to our estimates, the average depth of oocytes is 29, consistent with previous estimates. The average depth of B cells ranges from 34 to 79, linearly related to the mouse age, suggesting a rate of one cell division per day. In contrast, various types of adult stem cells underwent on average fewer cell divisions, supporting the notion that adult stem cells are relatively quiescent. Our method for depth estimation opens a window for revealing tissue turnover rates in animals, including humans, which has important implications for our knowledge of the body under physiological and pathological conditions.


Endocrinology | 2010

Epithelial cell transforming protein 2 (ECT2) depletion blocks polar body extrusion and generates mouse oocytes containing two metaphase II spindles.

Judith Elbaz; Yitzhak Reizel; Nava Nevo; Dalia Galiani; Nava Dekel

Completion of the first meiosis in oocytes is achieved by the extrusion of the first polar body (PBI), a particular example of cell division. In mitosis, the small GTPase RhoA, which is activated by epithelial cell transforming protein 2 (ECT2), orchestrates contractile ring constriction, thus enabling cytokinesis. However, the involvement of this pathway in mammalian oocytes has not been established. To characterize the role of ECT2 in PBI emission in mouse oocytes, the small interfering RNA approach was employed. We found that ECT2 depletion significantly reduces PBI emission, induces first metaphase arrest, and generates oocytes containing two properly formed spindles of the second metaphase. Moreover, we describe, for the first time, that before PBI emission, RhoA forms a ring that is preceded by a dome-like accumulation at the oocyte cortex, next to the spindle. This unique mode of RhoA translocation failed to occur in the absence of ECT2. We further found that the Rho-dependent kinase, a main RhoA effector, is essential for PBI emission. In addition, we demonstrate herein that ECT2 is subjected to phosphorylation/dephosphorylation throughout meiosis in oocytes and further reveal that PBI emission is temporally associated with ECT2 dephosphorylation. Our data provide the first demonstration that an active cyclin-dependent kinase 1, the catalytic subunit of the maturation-promoting factor, phosphorylates ECT2 during the first meiotic metaphase and that cyclin-dependent kinase 1 inactivation at anaphase allows ECT2 dephosphorylation. In conclusion, our study demonstrates the indispensable role of the maturation-promoting factor/ECT2/RhoA pathway in PBI extrusion in mouse oocytes.


The FASEB Journal | 2012

From ubiquitin-proteasomal degradation to CDK1 inactivation: requirements for the first polar body extrusion in mouse oocytes

Yael Pomerantz; Judith Elbaz; Inbal Ben-Eliezer; Yitzhak Reizel; Yael David; Dalia Galiani; Nava Nevo; Ami Navon; Nava Dekel

Completion of the first meiotic division, manifested by extrusion of the first polar body (PBI), depends on proteasomal degradation of cyclin B1 and securin and the subsequent respective CDK1 inactivation and chromosome segregation. We aimed at identifying the polyubiquitin signal that mediates proteasomal action and at a better characterization of the role of CDK1 inactivation at this stage of meiosis. Microinjections of mutated ubiquitin proteins into mouse oocytes revealed that interference with lysine‐11 polyubiquitin chains abrogated chromosome segregation and reduced PBI extrusion by 63% as compared to WT ubiquitin‐injected controls. Inactivation of CDK1 in oocytes arrested at first metaphase by a proteasome inhibitor fully rescued PBI extrusion. However, removal of CDK1 inhibition failed to allow progression to the second metaphase, rather, inducing PBI reengulfment in 62% of the oocytes. Inhibition of either PLK1 or MEK1/2 during the first anaphase changed spindle dimensions. The PLK1 inhibitor also blocked PBI emission and prevented RhoA translocation. Our results identified lysine‐11 rather than the canonic lysine‐48 ubiquitin chains as the degradation signal in oocytes resuming meiosis, further disclosing that CDK1 inactivation is necessary and sufficient for PBI emission. This information significantly contributes to our understanding of faulty chromosome segregation that may lead to aneuploidy.—Pomerantz, Y., Elbaz, J., Ben‐Eliezer, I., Reizel, Y., David, Y., Galiani, D., Nevo, N., Navon, A., Dekel, N. From ubiquitin‐proteasomal degradation to CDK1 inactivation: requirements for the first polar body extrusion in mouse oocytes. FASEB J. 26, 4495–4505 (2012). www.fasebj.org


PLOS ONE | 2011

Muscle-Bound Primordial Stem Cells Give Rise to Myofiber-Associated Myogenic and Non-Myogenic Progenitors

Elad Segev; Gabi Shefer; Rivka Adar; Noa Chapal-Ilani; Shalev Itzkovitz; Inna Horovitz; Yitzhak Reizel; Dafna Benayahu; Ehud Y. Shapiro

Myofiber cultures give rise to myogenic as well as to non-myogenic cells. Whether these myofiber-associated non-myogenic cells develop from resident stem cells that possess mesenchymal plasticity or from other stem cells such as mesenchymal stem cells (MSCs) remain unsolved. To address this question, we applied a method for reconstructing cell lineage trees from somatic mutations to MSCs and myogenic and non-myogenic cells from individual myofibers that were cultured at clonal density. Our analyses show that (i) in addition to myogenic progenitors, myofibers also harbor non-myogenic progenitors of a distinct, yet close, lineage; (ii) myofiber-associated non-myogenic and myogenic cells share the same muscle-bound primordial stem cells of a lineage distinct from bone marrow MSCs; (iii) these muscle-bound primordial stem-cells first part to individual muscles and then differentiate into myogenic and non-myogenic stem cells.


PLOS Computational Biology | 2013

Comparing algorithms that reconstruct cell lineage trees utilizing information on microsatellite mutations.

Noa Chapal-Ilani; Yosef E. Maruvka; Adam Spiro; Yitzhak Reizel; Rivka Adar; Liran I. Shlush; Ehud Shapiro

Organism cells proliferate and die to build, maintain, renew and repair it. The cellular history of an organism up to any point in time can be captured by a cell lineage tree in which vertices represent all organism cells, past and present, and directed edges represent progeny relations among them. The root represents the fertilized egg, and the leaves represent extant and dead cells. Somatic mutations accumulated during cell division endow each organism cell with a genomic signature that is unique with a very high probability. Distances between such genomic signatures can be used to reconstruct an organisms cell lineage tree. Cell populations possess unique features that are absent or rare in organism populations (e.g., the presence of stem cells and a small number of generations since the zygote) and do not undergo sexual reproduction, hence the reconstruction of cell lineage trees calls for careful examination and adaptation of the standard tools of population genetics. Our lab developed a method for reconstructing cell lineage trees by examining only mutations in highly variable microsatellite loci (MS, also called short tandem repeats, STR). In this study we use experimental data on somatic mutations in MS of individual cells in human and mice in order to validate and quantify the utility of known lineage tree reconstruction algorithms in this context. We employed extensive measurements of somatic mutations in individual cells which were isolated from healthy and diseased tissues of mice and humans. The validation was done by analyzing the ability to infer known and clear biological scenarios. In general, we found that if the biological scenario is simple, almost all algorithms tested can infer it. Another somewhat surprising conclusion is that the best algorithm among those tested is Neighbor Joining where the distance measure used is normalized absolute distance. We include our full dataset in Tables S1, S2, S3, S4, S5 to enable further analysis of this data by others.


Endocrine Reviews | 2010

Sustained Activity of the EGF Receptor Is an Absolute Requisite for LH-Induced Oocyte Maturation and Cumulus Expansion

Yitzhak Reizel; Judith Elbaz; Nava Dekel

Mammalian reproduction depends on the release of a mature oocyte from the ovarian follicle. Maturation of the oocyte and rupture of the follicle wall constitute part of the responses to the preovulatory surge of LH, which also include cumulus expansion and granulosa cell luteinization. It was previously shown that the epidermal growth factor receptor (EGFR) mediates the ovulatory response to LH in the ovarian follicle. We hypothesized that it is a sustained activity of the EGFR that generates oocyte maturation and cumulus expansion. We demonstrated that, whereas a transient exposure of rat isolated, intact, preovulatory follicles to either LH or forskolin was sufficient to induce oocyte maturation and cumulus expansion, these LH-induced responses were only generated upon a prolonged activity of the EGFR. In addition, the continuous activity of the EGFR is essential for the chronic phosphorylation of the ERK1/2 downstream signaling molecules, which were shown to be essential for oocyte maturation and cumulus expansion. Interestingly, EGFR-sustained activity was also necessary to maintain the up-regulation of Ptgs2, a gene essential for cumulus expansion. The unusual prolonged duration of ERK1/2 activity may possibly be attributed to the late induction of the ERK-specific phosphatase 3, demonstrated herein. These new data shed light on the unique characteristics of EGFR-ERK1/2 activity in the ovarian follicle and emphasize the fact that the ovulatory process involves a nonclassical activation of this pathway. (Molecular Endocrinology 24: 402–411, 2010)


Developmental Biology | 2008

Oocyte-directed depletion of connexin43 using the Cre-LoxP system leads to subfertility in female mice

Eran Gershon; Vicki Plaks; Idan Aharon; Dalia Galiani; Yitzhak Reizel; Sagit Sela-Abramovich; Irit Granot; Elke Winterhager; Nava Dekel

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Nava Dekel

Weizmann Institute of Science

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Judith Elbaz

Weizmann Institute of Science

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Rivka Adar

Weizmann Institute of Science

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Noa Chapal-Ilani

Weizmann Institute of Science

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Shalev Itzkovitz

Weizmann Institute of Science

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Dalia Galiani

Weizmann Institute of Science

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Ehud Y. Shapiro

Weizmann Institute of Science

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Nava Nevo

Weizmann Institute of Science

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