Abstract：
:Lineage specification of multipotent progenitor cells is governed by a balance of lineage-affiliated transcription factors, such as GATA1 and PU.1, which regulate the choice between erythroid and myelomonocytic fates. But how ratios of lineage-determining transcription factors stabilize progenitor cells and resolve their indeterminacy to commit them to discrete, mutually exclusive fates remains unexplained. We used a simple model and experimental measurements to analyze the dynamics of a binary fate decision governed by a gene-circuit containing auto-stimulation and cross-inhibition, as embodied by the GATA1-PU.1 paradigm. This circuit generates stable attractors corresponding to erythroid and myelomonocytic fates, as well as an uncommitted metastable state characterized by coexpression of both regulators, explaining the phenomenon of "multilineage priming". GATA1 and PU.1 mRNA and transcriptome dynamics of differentiating progenitor cells confirm that commitment occurs in two stages, as suggested by the model: first, the progenitor state is destabilized in an almost symmetrical bifurcation event, resulting in a poised state at the boundary between the two lineage-specific attractors; second, the cell is driven to the respective, now accessible attractors. This minimal model captures fundamental features of binary cell fate decisions, uniting the concepts of stochastic (selective) and deterministic (instructive) regulation, and hence, may apply to a wider range of binary fate decision points.
journal_name
Dev Bioljournal_title
Developmental biologyauthors
Huang S,Guo YP,May G,Enver Tdoi
10.1016/j.ydbio.2007.02.036subject
Has Abstractpub_date
2007-05-15 00:00:00pages
695-713issue
2eissn
0012-1606issn
1095-564Xpii
S0012-1606(07)00167-4journal_volume
305pub_type
杂志文章abstract：:Transcription factors (TFs) can regulate different sets of genes to determine specific cell types by means of combinatorial codes. We previously identified closely-spaced TF binding motifs located 8.2-8.5 kb 5' to the ATG of the murine Pou4f3 gene, a gene required for late hair cell (HC) differentiation and survival. ...
journal_title：Developmental biology
pub_type： 杂志文章
doi：10.1016/j.ydbio.2012.09.002
更新日期：2012-12-01 00:00:00
abstract：:The shoot meristem generates all of the aerial structures of an adult plant. It is organized in three layers which produce the epidermis (L1 layer) and the subepidermal layers (L2 and L3). The origin of adult structures has previously been fate mapped to the primary meristem for L2 and L3 tissues. In this work we cons...
journal_title：Developmental biology
pub_type： 杂志文章
doi：10.1006/dbio.1996.0112
更新日期：1996-05-01 00:00:00
abstract：:Hippo (Hpo) signaling plays a critical role in restricting tissue growth and organ size in both invertebrate and vertebrate animals. However, how the Hpo kinase is regulated during development has not been clearly understood. Using a Bimolecular Fluorescence Complementation assay, we have investigated the functional s...
journal_title：Developmental biology
pub_type： 杂志文章
doi：10.1016/j.ydbio.2012.12.017
更新日期：2013-03-15 00:00:00
abstract：:Previous studies have shown that cultured Schwann cells secrete platelet-derived growth factor (PDGF) and express PDGF receptors which transmit a mitogenic response particularly when their levels are upregulated by elevation of intracellular cAMP. In this study the expression of PDGF and PDGF alpha- and beta-receptors...
journal_title：Developmental biology
pub_type： 杂志文章
doi：10.1006/dbio.1993.1044
更新日期：1993-02-01 00:00:00
abstract：:Germ line transformation has been used to map the cis regulatory DNA elements responsible for the precise and evolutionarily stable developmental expression of the s18 chorion gene. Constructs containing chimeric combinations of Drosophila melanogaster and D. grimshawi DNA regions, as well as D. grimshawi sequences al...
journal_title：Developmental biology
pub_type： 杂志文章
doi：10.1016/0012-1606(92)90160-i
更新日期：1992-07-01 00:00:00
abstract：:A number of genes encoding developmentally regulated mRNAs in the cellular slime mold, Dictyostelium discoideum, have been described. Many of these are regulated by cAMP. Analysis of the earliest time at which elevated levels of cAMP can induce the expression of these mRNAs reveals a more complex pattern of regulation...
journal_title：Developmental biology
pub_type： 杂志文章
doi：10.1016/0012-1606(86)90323-4
更新日期：1986-10-01 00:00:00
abstract：:During early vertebrate development, members of the transforming growth factor beta (TGFbeta) family play important roles in a variety of processes, including germ layer specification, patterning, cell differentiation, migration, and organogenesis. The activities of TGFbetas need to be tightly controlled to ensure the...
journal_title：Developmental biology
pub_type： 杂志文章
doi：10.1016/s0012-1606(02)00075-1
更新日期：2003-03-01 00:00:00
abstract：:G protein Galpha subunits contribute to the specificity of different signal transduction pathways in Dictyostelium discoideum but Galpha subunit-effector interactions have not been previously identified. The requirement of the Dictyostelium Galpha4 subunit for MAP kinase (MAPK) activation and the identification of a p...
journal_title：Developmental biology
pub_type： 杂志文章
doi：10.1016/j.ydbio.2009.09.011
更新日期：2009-11-15 00:00:00
abstract：:Sea urchin eggs secrete a serine protease activity, CGSP1, at fertilization that is essential for the block to polyspermy. Several targets of this proteolytic activity on the plasma membrane were identified here using a cell surface biotinylation approach. Amino acid microsequencing of one of these proteins led to the...
journal_title：Developmental biology
pub_type： 杂志文章
doi：10.1016/j.ydbio.2004.03.043
更新日期：2004-08-01 00:00:00
abstract：:Cis-regulatory modules (CRMs) control spatiotemporal gene expression patterns in embryos. While measurement of quantitative CRM activities has become efficient, measurement of spatial CRM activities still relies on slow, one-by-one methods. To overcome this bottleneck, we have developed a high-throughput method that c...
journal_title：Developmental biology
pub_type： 杂志文章
doi：10.1016/j.ydbio.2017.01.010
更新日期：2017-02-15 00:00:00
abstract：:Caenorhabditis elegans PEB-1 is a novel DNA-binding protein expressed in most pharyngeal cell types and outside the pharynx in the hypodermis, hindgut, and vulva. Previous RNAi analyses indicated that PEB-1 is required for normal morphology of these tissues and growth; however, the peb-1 null phenotype was unknown. He...
journal_title：Developmental biology
pub_type： 杂志文章
doi：10.1016/j.ydbio.2004.08.040
更新日期：2004-12-15 00:00:00
abstract：:Caenorhabditis elegans embryonic elongation depends on both epidermal and muscle cells. The hemidesmosome-like junctions, commonly called fibrous organelles (FOs), that attach the epidermis to the extracellular matrix ensure muscle anchoring to the cuticular exoskeleton and play an essential role during elongation. To...
journal_title：Developmental biology
pub_type： 杂志文章
doi：10.1016/j.ydbio.2010.11.025
更新日期：2011-02-15 00:00:00
abstract：:We have isolated Xbr-1, a novel Xenopus homeobox gene that defines a new class of homeobox genes, distantly related to the Drosophila BarH1 and BarH2 genes. Xbr-1 is predominantly expressed in the developing Xenopus eye, starting as early as the neural plate stage. At early stages of eye development XBR-1 is expressed...
journal_title：Developmental biology
pub_type： 杂志文章
doi：10.1006/dbio.1996.0055
更新日期：1996-02-25 00:00:00
abstract：:Newts regenerate lost limbs through a complex process involving dedifferentiation, migration, proliferation, and redifferentiation of cells proximal to the amputation plane. To identify the genes controlling these cellular events, we performed a differential display analysis between regenerating and nonregenerating li...
journal_title：Developmental biology
pub_type： 杂志文章
doi：10.1016/j.ydbio.2004.12.003
更新日期：2005-03-01 00:00:00
abstract：:The ability to express exogenous reporter genes in intact, externally developing embryos, such as Xenopus, is a powerful tool for characterizing the activity of cis-regulatory gene elements during development. Although methods exist for generating transgenic Xenopus lines, more simplified methods for use with F0 anima...
journal_title：Developmental biology
pub_type： 杂志文章
doi：10.1016/j.ydbio.2014.11.010
更新日期：2015-02-01 00:00:00
abstract：:The cellular mechanisms underlying the amazing ability of sea cucumbers to regenerate their autotomized intestines have been widely described by us and others. However, the signaling pathways that control these mechanisms are unknown. Previous studies have shown that Wnt homologs are upregulated during early intestina...
journal_title：Developmental biology
pub_type： 杂志文章
doi：10.1016/j.ydbio.2019.10.005
更新日期：2020-02-01 00:00:00
abstract：:The facial primordia in the chick embryo begin as rounded swellings that surround the primitive mouth and these grow out to form the beak. The control of proximodistal outgrowth is not well understood but may involve similar mechanisms to the limb bud. In order to test this hypothesis, combinations were made between e...
journal_title：Developmental biology
pub_type： 杂志文章
doi：10.1016/0012-1606(92)90069-s
更新日期：1992-12-01 00:00:00
abstract：:Conjugation in Tetrahymena represents an ordered developmental pathway which represents the sexual phase of the ciliate life cycle. This pathway is initiated when starved cells of opposite mating types are mixed and are allowed to make a series of cell-cell contacts (a period termed costimulation) which lead to the fo...
journal_title：Developmental biology
pub_type： 杂志文章
doi：10.1016/0012-1606(91)90075-e
更新日期：1991-02-01 00:00:00
abstract：:Mammalian heart development involves complex morphogenetic events which lead to the formation of fully separated left and right atrial and ventricular chambers from a tubular heart. Separation of left and right ventricular chambers is dependent on a single structure, the interventricular septum (IVS), which has both m...
journal_title：Developmental biology
pub_type： 杂志文章
doi：10.1016/j.ydbio.2006.02.045
更新日期：2006-06-15 00:00:00
abstract：:Primitive blood constitutes the ventralmost mesoderm in amphibians, and its cleavage-stage origin reveals important clues about the orientation of the dorsal/ventral axis in the embryo. In recent years, investigators employing various lineage-labeling strategies have reported disparate results for the origin of primit...
journal_title：Developmental biology
pub_type： 杂志文章
doi：10.1006/dbio.2002.0717
更新日期：2002-08-01 00:00:00
abstract：:A modification of the scrape-loading/dye transfer technique was used to study gap junctional communication along the anterior-posterior (A-P) axis of embryonic chick wing buds at an early stage of development (stage 20/21) when positional values along the A-P axis are being specified. Extensive intercellular transfer ...
journal_title：Developmental biology
pub_type： 杂志文章
doi：10.1016/0012-1606(91)90271-4
更新日期：1991-12-01 00:00:00
abstract：:Development of the mammalian external genitalia is controlled by a network of signaling molecules and transcription factors. Because FGF signaling plays a central role in this complicated morphogenetic process, we investigated the role of Sprouty genes, which are important intracellular modulators of FGF signaling, du...
journal_title：Developmental biology
pub_type： 杂志文章
doi：10.1016/j.ydbio.2013.12.014
更新日期：2014-02-01 00:00:00
abstract：:A small number of signaling pathways are used repeatedly during organogenesis, and they can have drastically different effects on the same population of cells depending on the embryonic stage. How cellular competence changes over developmental time is not well understood. Here we used Xenopus, mouse, and human pluripo...
journal_title：Developmental biology
pub_type： 杂志文章
doi：10.1016/j.ydbio.2017.11.018
更新日期：2018-02-01 00:00:00
abstract：:Gastrulation in Xenopus laevis transforms a ball of undifferentiated cells into a well-organized elongated embryo with a distinct body axis, as a result of extensive cell rearrangements and movements. Since cell adhesion is thought to play an important role during tissue morphogenesis, we investigated the potential ro...
journal_title：Developmental biology
pub_type： 杂志文章
doi：10.1006/dbio.1995.1288
更新日期：1995-10-01 00:00:00
abstract：:The Endo16 gene codes for an RGD-containing calcium-binding protein that is found on the basal surfaces and in the extracellular matrix of cells of the invaginating archenteron during sea urchin gastrulation. Previously, we have shown that Endo16 is a single copy gene and we have determined the coding sequence and ana...
journal_title：Developmental biology
pub_type： 杂志文章
doi：10.1006/dbio.1996.0247
更新日期：1996-10-10 00:00:00
abstract：:Cloning and sequencing of Tripneustes gratilla genomic DNA and cDNA encoding a developmentally regulated, embryonic messenger RNA, referred to as Tg616, revealed an actin-encoding gene orthologous to the CyI actin gene described from Strongylocentrotus purpuratus. Tg616 and SpCyI share: (1) 150 nucleotides of highly c...
journal_title：Developmental biology
pub_type： 杂志文章
doi：10.1006/dbio.1994.1239
更新日期：1994-09-01 00:00:00
abstract：:To feed or breathe, the oral opening must connect with the gut. The foregut and oral tissues converge at the primary mouth, forming the buccopharyngeal membrane (BPM), a bilayer epithelium. Failure to form the opening between gut and mouth has significant ramifications, and many craniofacial disorders have been associ...
journal_title：Developmental biology
pub_type： 杂志文章
doi：10.1016/j.ydbio.2014.09.029
更新日期：2014-12-01 00:00:00
abstract：:Much progress has been made in elucidating the molecular networks required for specifying retinal cells, including photoreceptors, but the downstream mechanisms that maintain identity and regulate differentiation remain poorly understood. Here, we report that the transcription factor Glass has a dual role in establish...
journal_title：Developmental biology
pub_type： 杂志文章
doi：10.1016/j.ydbio.2016.04.012
更新日期：2016-06-01 00:00:00
abstract：:A glycoprotein from the liver, which shares epitopes with chorion (egg envelope or zona pellucida) glycoproteins, is present only in the spawning female fish, Oryzias latipes, under natural conditions. This spawning female-specific (SF) substance is distinct from vitellogenin but closely resembles a major glycoprotein...
journal_title：Developmental biology
pub_type： 杂志文章
doi：10.1016/0012-1606(89)90301-1
更新日期：1989-05-01 00:00:00
abstract：:Metaphase II arrest of Xenopus oocyte is characterized by the presence of M-phase-promoting factor (MPF) and of a microtubular spindle, both of which are stable in the presence of protein synthesis inhibitors. We studied in vivo this equilibrium state that is settled during meiotic maturation. At time of germinal vesi...
journal_title：Developmental biology
pub_type： 杂志文章
doi：10.1006/dbio.1997.8543
更新日期：1997-05-01 00:00:00
