scholarly journals Induction of mouse germ-cell fate by transcription factors in vitro

Nature ◽  
2013 ◽  
Vol 501 (7466) ◽  
pp. 222-226 ◽  
Author(s):  
Fumio Nakaki ◽  
Katsuhiko Hayashi ◽  
Hiroshi Ohta ◽  
Kazuki Kurimoto ◽  
Yukihiro Yabuta ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Germ Cell ◽  
Cell Fate

scholarly journals GATA transcription factors, SOX17 and TFAP2C, drive the human germ-cell specification program

2021 ◽  
Vol 4 (5) ◽  
pp. e202000974
Author(s):  
Yoji Kojima ◽  
Chika Yamashiro ◽  
Yusuke Murase ◽  
Yukihiro Yabuta ◽  
Ikuhiro Okamoto ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Germ Cell ◽  
Cell Fate ◽  
Germ Line ◽  
Primordial Germ Cell ◽  
Bmp Signaling ◽  
Germ Cell Specification ◽  
Bona Fide ◽  
Underlying Mechanisms

The in vitro reconstitution of human germ-cell development provides a robust framework for clarifying key underlying mechanisms. Here, we explored transcription factors (TFs) that engender the germ-cell fate in their pluripotent precursors. Unexpectedly, SOX17, TFAP2C, and BLIMP1, which act under the BMP signaling and are indispensable for human primordial germ-cell-like cell (hPGCLC) specification, failed to induce hPGCLCs. In contrast, GATA3 or GATA2, immediate BMP effectors, combined with SOX17 and TFAP2C, generated hPGCLCs. GATA3/GATA2 knockouts dose-dependently impaired BMP-induced hPGCLC specification, whereas GATA3/GATA2 expression remained unaffected in SOX17, TFAP2C, or BLIMP1 knockouts. In cynomolgus monkeys, a key model for human development, GATA3, SOX17, and TFAP2C were co-expressed exclusively in early PGCs. Crucially, the TF-induced hPGCLCs acquired a hallmark of bona fide hPGCs to undergo epigenetic reprogramming and mature into oogonia/gonocytes in xenogeneic reconstituted ovaries. By uncovering a TF circuitry driving the germ line program, our study provides a paradigm for TF-based human gametogenesis.

Porcine nuclear transfer using somatic donor cells altered to express male germ cell function

2009 ◽  
Vol 21 (7) ◽  
pp. 882 ◽  
Author(s):  
Sangho Roh ◽  
Hye-Yeon Choi ◽  
Sang Kyu Park ◽  
Cheolhee Won ◽  
Bong-Woo Kim ◽  
...  
Keyword(s):  
Germ Cell ◽  
Cell Fate ◽  
Nuclear Transfer ◽  
Cell Function ◽  
Control Cell ◽  
Donor Cell ◽  
Male Germ Cell ◽  
Cell Group ◽  
Cell Extracts

Recent studies reported that the direct transformation of one differentiated somatic cell type into another is possible. In the present study, we were able to modulate the cell fate of somatic cells to take on male germ cell function by introducing cell extracts derived from porcine testis tissue. Fibroblasts were treated with streptolysin O, which reversibly permeabilises the plasma membrane, and incubated with testis extracts. Our results showed that the testis extracts (TE) could activate expression of male germ cell-specific genes, implying that TE can provide regulatory components required for altering the cell fate of fibroblasts. Male germ cell function was sustained for more than 10 days after the introduction of TE. In addition, a single TE-treated cell was injected directly into the cytoplasm of in vitro-matured porcine oocytes. The rate of blastocyst formation was significantly higher in the TE-treated nuclear donor cell group than in the control cell group. The expression level of Nanog, Sox9 and Eomes was drastically increased when altered cells were used as donor nuclei. Our results suggest that TE can be used to alter the cell fate of fibroblasts to express male germ cell function and improve the developmental efficiency of the nuclear transfer porcine embryos.

scholarly journals Regulation of E2F1-Dependent Gene Transcription and Apoptosis by the ETS-Related Transcription Factor GABPγ1

2002 ◽  
Vol 22 (7) ◽  
pp. 2147-2158 ◽  
Author(s):  
Ludger Hauck ◽  
Rudolf G. Kaba ◽  
Martin Lipp ◽  
Rainer Dietz ◽  
Rüdiger von Harsdorf
Keyword(s):  
Transcription Factor ◽  
Transcription Factors ◽  
Cell Fate ◽  
Binding Domain ◽  
Pocket Proteins ◽  
Related Transcription Factor ◽  
Terminal Amino ◽  
Fate Decision

ABSTRACT The E2F family of transcription factors comprises six related members which are involved in the control of the coordinated progression through the G1/S-phase transition of cell cycle or in cell fate decision. Their activity is regulated by pocket proteins, including pRb, p107, and p130. Here we show that E2F1 directly interacts with the ETS-related transcription factor GABPγ1 in vitro and in vivo. The binding domain interacting with GABPγ1 was mapped to the C-terminal amino acids 310 to 437 of E2F1, which include its transactivation and pRb binding domain. Among the E2F family of transcription factors, the interaction with GABPγ1 is restricted to E2F1. DNA-binding E2F1 complexes containing GABPγ1 are characterized by enhanced E2F1-dependent transcriptional activity. Moreover, GABPγ1 suppresses E2F1-dependent apoptosis by mechanisms other than the inhibition of the transactivation capacity of E2F1. In summary, our results provide evidence for a novel pRb-independent mechanism regulating E2F1-dependent transcription and apoptosis.

Epigenetic regulation in stem cell development, cell fate conversion, and reprogramming

2015 ◽  
Vol 6 (1) ◽  
pp. 1-9 ◽  
Author(s):  
Kazuyuki Ohbo ◽  
Shin-ichi Tomizawa
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Transcription Factors ◽  
Cell Fate ◽  
Cell Lines ◽  
Cell Fate Decisions ◽  
Micro Rnas ◽  
Stem Cell Lines ◽  
Cell Fate Conversion

AbstractStem cells are identified classically by an in vivo transplantation assay plus additional characterization, such as marker analysis, linage-tracing and in vitro/ex vivo differentiation assays. Stem cell lines have been derived, in vitro, from adult tissues, the inner cell mass (ICM), epiblast, and male germ stem cells, providing intriguing insight into stem cell biology, plasticity, heterogeneity, metastable state, and the pivotal point at which stem cells irreversibly differentiate to non-stem cells. During the past decade, strategies for manipulating cell fate have revolutionized our understanding about the basic concept of cell differentiation: stem cell lines can be established by introducing transcription factors, as with the case for iPSCs, revealing some of the molecular interplay of key factors during the course of phenotypic changes. In addition to de-differentiation approaches for establishing stem cells, another method has been developed whereby induced expression of certain transcription factors and/or micro RNAs artificially converts differentiated cells from one committed lineage to another; notably, these cells need not transit through a stem/progenitor state. The molecular cues guiding such cell fate conversion and reprogramming remain largely unknown. As differentiation and de-differentiation are directly linked to epigenetic changes, we overview cell fate decisions, and associated gene and epigenetic regulations.

scholarly journals Simulating gastrulation development and germ cell fate in vitro using human and monkey pluripotent stem cells

2017 ◽  
Author(s):  
Toshihiro Kobayashi ◽  
Toshihiro Kobayashi ◽  
Ramiro Alberio ◽  
M Azim Surani
Keyword(s):  
Stem Cells ◽  
Germ Cell ◽  
Cell Fate ◽  
Pluripotent Stem Cells

scholarly journals LEAFY is a pioneer transcription factor and licenses cell reprogramming to floral fate

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Run Jin ◽  
Samantha Klasfeld ◽  
Yang Zhu ◽  
Meilin Fernandez Garcia ◽  
Jun Xiao ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Transcription Factors ◽  
Cell Fate ◽  
Chromatin Accessibility ◽  
Binding Motifs ◽  
Chromatin Remodelers ◽  
Pioneer Transcription Factor ◽  
Chromatin Reprogramming

AbstractMaster transcription factors reprogram cell fate in multicellular eukaryotes. Pioneer transcription factors have prominent roles in this process because of their ability to contact their cognate binding motifs in closed chromatin. Reprogramming is pervasive in plants, whose development is plastic and tuned by the environment, yet little is known about pioneer transcription factors in this kingdom. Here, we show that the master transcription factor LEAFY (LFY), which promotes floral fate through upregulation of the floral commitment factor APETALA1 (AP1), is a pioneer transcription factor. In vitro, LFY binds to the endogenous AP1 target locus DNA assembled into a nucleosome. In vivo, LFY associates with nucleosome occupied binding sites at the majority of its target loci, including AP1. Upon binding, LFY ‘unlocks’ chromatin locally by displacing the H1 linker histone and by recruiting SWI/SNF chromatin remodelers, but broad changes in chromatin accessibility occur later. Our study provides a mechanistic framework for patterning of inflorescence architecture and uncovers striking similarities between LFY and animal pioneer transcription factor.

scholarly journals LEAFY is a pioneer transcription factor and licenses cell reprogramming to floral fate

2020 ◽  
Author(s):  
Run Jin ◽  
Samantha Klasfeld ◽  
Meilin Fernandez Garcia ◽  
Jun Xiao ◽  
Soon-Ki Han ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Transcription Factors ◽  
Cell Fate ◽  
Chromatin Accessibility ◽  
Binding Motifs ◽  
Chromatin Remodelers ◽  
Pioneer Transcription Factor ◽  
Chromatin Reprogramming

ABSTRACTMaster transcription factors reprogram cell fate in multicellular eukaryotes. Pioneer transcription factors have prominent roles in this process because of their ability to contact their cognate binding motifs in closed chromatin. Reprogramming is pervasive in plants, whose development is plastic and tuned by the environment, yet no bonafide pioneer transcription factor has - been identified in this kingdom. Here we show that the master transcription factor LEAFY (LFY), which promotes floral fate through upregulation of the floral commitment factor APETALA1 (AP1), is a pioneer transcription factor. In vitro, LFY binds in a sequence-specific manner and with high affinity to the endogenous AP1 target locus DNA assembled into a nucleosome. In vivo, LFY associates with nucleosome occupied binding sites at the majority of its target loci, including AP1, where it co-occupies DNA with histones. Moreover, the LFY DNA contact helix shares defining properties with those of strong nucleosome binding pioneer factors. At the AP1 locus, LFY unlocks chromatin locally by displacing the H1 linker histone and by recruiting SWI/SNF chromatin remodelers, but broad changes in chromatin accessibility occur later and require activity of additional, non-pioneer transcription, factors. Our study provides a mechanistic framework for patterning of inflorescence architecture and uncovers striking similarities between plant and animal pioneer transcription factors. Further analyses aimed at elucidating the defining characteristics of pioneer transcription factors will allow harnessing these for enhanced cell fate reprogramming.

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