Zfx Controls the Self-Renewal of Embryonic and Hematopoietic Stem Cells

Galán-Caridad, José M.; Harel, Sivan; Arenzana, Teresita L.; Hou, Zhonggang; Doetsch, Fiona; Mirny, Leonid A.; Reizis, Boris

doi:10.1016/j.cell.2007.03.014

Cited by 218 publications

(219 citation statements)

References 41 publications

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“…If the expression of Tcl1 is maintained constantly within the same cells, as it seems to be in other tissues such as B cells and embryo, it would implicate that proliferating cells that derive from HG-cells, during catagen-telogen transition, are those starting the new HF cycle and repopulating the bulge ( Figure 5). As in the embryo, where Tcl1 is necessary in the first divisions of proliferating cells of the preimplantation embryo, and for self-renewal but not differentiation of their derived ES-cells (Matoba et al, 2006;Galan-Caritad et al, 2007) in the HF, Tcl1 is important very early during the anagen proliferation of secondary HG-cells, as beyond the third day after depilation the expression of Tcl1 is no more detectable.…”

Section: Discussionmentioning

confidence: 99%

“…In particular, it plays an important role in the latter as, in Tcl1 À/À mice, preimplantation embryos are not able to progress beyond the 4-cell stage, in vitro (Narducci et al, 2002). In ES cells, Tcl1 acts in proliferation and normal self-renewal under the direct activation of OCT3/4, Zfx and KLF5 transcription factors (Matoba et al, 2006;Galan-Caritad et al, 2007;Ema et al, 2008). Therefore, Tcl1 is not ubiquitously expressed, but seems to be tightly regulated in cells that undergo different waves of proliferative signals to complete their differentiation programs: pro-B cells in the bone marrow, the mantle lymphocytes of peripheral lymph nodes in which B cells must encounter the antigen and go through new waves of mitosis, the fertilized egg before zygotic gene activation when the cell, still under maternal control, must divide rapidly after having been blocked in metaphase II for a long time and ES cells.…”

Section: Introductionmentioning

confidence: 99%

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The Tcl1 oncogene defines secondary hair germ cells differentiation at catagen–telogen transition and affects stem-cell marker CD34 expression

et al. 2009

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Overexpression of the TCL1 gene family plays a role in the onset of T-cell leukemias in mice and in humans. The Tcl1 gene is tightly regulated during early embryogenesis in which it participates in embryonic stem (ES)-cells proliferation and during lymphoid differentiation. Here, we provide evidences that Tcl1 is also important in mouse hair follicle (HF) and skin homeostasis. We found that Tcl1 À/À adult mice exhibit hair loss, leading to alopecia with extensive skin lesions. By analysing Tcl1 expression in the wild-type (wt) skin through different stages of hair differentiation, we observe high levels in the secondary hair germ (HG) cells and hair bulges, during early anagen and catagen-telogen transition phases. The loss of Tcl1 does not result in apparent skin morphological defects during embryonic development and at birth, but its absence causes a reduction of proliferation in anagen HFs. Importantly, we show the that absence of Tcl1 induces a significant loss of the stem-cell marker CD34 (but not a6-integrin) expression in the bulge cells, which is necessary to maintain stem-cell characteristics. Therefore, our findings indicate that Tcl1 gene(s) might have important roles in hair formation, by its involvement in cycling and self-renewal of transient amplifying (TA) and stem-cell (SC) populations.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The Tcl1 oncogene defines secondary hair germ cells differentiation at catagen–telogen transition and affects stem-cell marker CD34 expression

et al. 2009

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“…Thus, both under-and overexpressed gene sets during adaptation were found to be enriched in a TFBS of ZFX ( Figure 4a, bottom panels), a transcription factor involved in stem cell self-renewal (Galan-Caridad et al, 2007). The underexpressed set was found to be enriched in TFBSs principally of the interferon regulatory transcription factor (IRF) family (Figure 4a).…”

Section: Effect Of 17be2 Through Eramentioning

confidence: 99%

Biological reprogramming in acquired resistance to endocrine therapy of breast cancer

et al. 2010

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Endocrine therapies targeting the proliferative effect of 17b-estradiol through estrogen receptor a (ERa) are the most effective systemic treatment of ERa-positive breast cancer. However, most breast tumors initially responsive to these therapies develop resistance through molecular mechanisms that are not yet fully understood. The longterm estrogen-deprived (LTED) MCF7 cell model has been proposed to recapitulate acquired resistance to aromatase inhibitors in postmenopausal women. To elucidate this resistance, genomic, transcriptomic and molecular data were integrated into the time course of MCF7-LTED adaptation. Dynamic and widespread genomic changes were observed, including amplification of the ESR1 locus consequently linked to an increase in ERa. Dynamic transcriptomic profiles were also observed that correlated significantly with genomic changes and were predicted to be influenced by transcription factors known to be involved in acquired resistance or cell proliferation (for example, interferon regulatory transcription factor 1 and E2F1, respectively) but, notably, not by canonical ERa transcriptional function. Consistently, at the molecular level, activation of growth factor signaling pathways by EGFR/ERBB/AKT and a switch from phospho-Ser118 (pS118)-to pS167-ERa were observed during MCF7-LTED adaptation. Evaluation of relevant clinical settings identified significant associations between MCF7-LTED and breast tumor transcriptome profiles that characterize ERa-negative status, early response to letrozole and tamoxifen, and recurrence after tamoxifen treatment. In accordance with these profiles, MCF7-LTED cells showed increased sensitivity to inhibition of FGFR-mediated signaling with PD173074. This study provides mechanistic insight into acquired resistance to endocrine therapies of breast cancer and highlights a potential therapeutic strategy.

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“…17 Then, the effect of siRNA-induced downregulation of ZFX on the cell cycle progression of PC-3 cells was analyzed using FACS ( Figure 4a). In the control group, the G1 and S phase accounted for cell percentages of 51% and 34%, respectively.…”

Section: Expression Of Zfx Was Suppressed By Infection Withmentioning

confidence: 99%

Knockdown of zinc finger protein X-linked inhibits prostate cancer cell proliferation and induces apoptosis by activating caspase-3 and caspase-9

et al. 2012

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Zinc finger protein X-linked (ZFX) is a highly conservative mammalian gene with related functions in cell survival and proliferation. However, there are limited reports on regulation of ZFX as a therapeutic target in cancer treatment. In this study, the expression of ZFX in prostate cancer with matched normal adjacent tissues (n ¼ 45) and benign prostatic hyperplasia (BPH) tissues (n ¼ 16) were observed by immunohistochemical analysis. The effect of lentiviral siRNA (small interference RNA)-mediated dysfunction of ZFX on the proliferation of prostate cancer cells was studied. ZFX mRNA and protein expression levels in prostate cancer cells (PC-3 and DU145) were analyzed by western blotting and real-time polymerase chain reaction (RT-PCR). The effects of siRNA targeting ZFX on growth, cell cycle and apoptosis of PC-3 cells were evaluated by MTT assay and flow cytometry. We also investigated the effect of ZFX deletion on the activation of caspase-1, -3 and -9 by western blotting and colorimetric assay. Prostate cancer specimens appeared significantly higher (42.2% of cases being positive) than that observed in normal adjacent tissues (11.8% of cases being positive) and BPH tissues (12.5% of cases being positive). Repression of ZFX in the prostate cancer cells effectively suppressed the cellular proliferation and colony-formation ability, and led to G1 phase cell cycle arrest. Moreover, inhibition of ZFX-induced cell apoptosis by activating caspase-1, -3 and -9. In conclusion, ZFX represents the prominent role in the progression of prostate cancer and may be a promising therapy target for prostate cancer.

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Zfx Controls the Self-Renewal of Embryonic and Hematopoietic Stem Cells

Cited by 218 publications

References 41 publications

The Tcl1 oncogene defines secondary hair germ cells differentiation at catagen–telogen transition and affects stem-cell marker CD34 expression

The Tcl1 oncogene defines secondary hair germ cells differentiation at catagen–telogen transition and affects stem-cell marker CD34 expression

Biological reprogramming in acquired resistance to endocrine therapy of breast cancer

Knockdown of zinc finger protein X-linked inhibits prostate cancer cell proliferation and induces apoptosis by activating caspase-3 and caspase-9

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