Structural-Change-Induced Two-Stage Redox Behavior of Pentacenebisquinodimethane with Tricolor Chromism.

Tricolor electrochromism was realized through the interconversion among the neutral (yellow), dicationic (green), and tetracationic (blue) states, even though only one kind of chromophore is generated upon oxidation. Both dicationic and tetracationic states were isolated as stable salts, and their different colors come from the effective inter-chromophore interaction only in the tetracationic state but not in the dicationic state. Despite the negligible Coulombic repulsion in the tetracationic state with four cyanine-type chromophores, pentacenebisquinodimethane undergoes stepwise two-stage two-electron oxidation when radical-stabilizing 5-(4-octyloxyphenyl)-2-thienyl groups are attached on the exomethylene bonds.

Thermal Equilibrium Between Quinoid/Biradical Forms Enhancing Electrochemical Amphotericity.

Upon dibenzo annulation on Thiele's hydrocarbon (tetraphenyl-p-quinodimethane), the quinoid form and the biradical form adopt quite different geometries, and thus are no longer resonance structures. When these two forms can interconvert rapidly due to the small energy barrier (ΔG), the equilibrated mixture contains both forms in a ratio that is determined by the energy difference (ΔG) between the two forms. For a series of tetrakis[5-(4-methoxyphenyl)-2-thienyl]-substituted derivatives, the more stable quinoid form and the metastable biradical form coexist in solution as an equilibrated mixture due to small ΔG (<15 kcal mol) and ΔG (1-4 kcal mol), in which the proportion of the two forms can be regulated by temperature.

p600 Plays Essential Roles in Fetal Development.

p600 is a multifunctional protein implicated in cytoskeletal organization, integrin-mediated survival signaling, calcium-calmodulin signaling and the N-end rule pathway of ubiquitin-proteasome-mediated proteolysis. While push, the Drosophila counterpart of p600, is dispensable for development up to adult stage, the role of p600 has not been studied during mouse development. Here we generated p600 knockout mice to investigate the in vivo functions of p600.

FLT3-ITD up-regulates MCL-1 to promote survival of stem cells in acute myeloid leukemia via FLT3-ITD-specific STAT5 activation.

Myeloid cell leukemia-1 (MCL-1) is an essential survival factor for hematopoiesis. In humans, hematopoietic stem cells (HSCs) express MCL-1 at the highest level in response to FMS-like tyrosine kinase-3 (FLT3) signaling. We here show that this FLT3-dependent stem cell maintenance system also plays a critical role in survival of leukemic stem cells (LSCs) in acute myeloid leukemia (AML).

Cyclin A is redundant in fibroblasts but essential in hematopoietic and embryonic stem cells.

Cyclins are regulatory subunits of cyclin-dependent kinases. Cyclin A, the first cyclin ever cloned, is thought to be an essential component of the cell-cycle engine. Mammalian cells encode two A-type cyclins, testis-specific cyclin A1 and ubiquitously expressed cyclin A2.

Reciprocal activation of GATA-1 and PU.1 marks initial specification of hematopoietic stem cells into myeloerythroid and myelolymphoid lineages.

A hierarchical hematopoietic development with myeloid versus lymphoid bifurcation has been proposed downstream of the multipotent progenitor (MPP) stage, based on prospective isolation of progenitors capable of generating only myeloerythroid cells (common myeloid progenitor, CMP) or only lymphocytes (common lymphoid progenitor, CLP). By utilizing GATA-1 and PU.1 transcription factor reporters, here we identified progenitor populations that are precursors for either CMPs or CLPs.

The order of expression of transcription factors directs hierarchical specification of hematopoietic lineages.

The mechanism of lineage specification in multipotent stem cells has not been fully understood. We recently isolated progenitors with the eosinophil, basophil, or mast cell lineage potential, all of which originate from granulocyte/monocyte progenitors (GMPs). By using these prospectively purified progenitors, we show here that the expression timing of GATA-2 and CCAAT enhancer-binding protein alpha (C/EBPalpha) can differentially control their lineage commitment.

C/EBPbeta is required for 'emergency' granulopoiesis.

During 'emergency' situations such as infections, host defense requires rapid mobilization of bone marrow granulocyte progenitors. 'Steady-state' granulopoiesis is absolutely dependent on the C/EBPalpha transcription factor, but the transcriptional mechanisms underlying emergency granulopoiesis remain unclear. Here we show that large numbers of granulocytes were generated from C/EBPalpha-deficient progenitors after cytokine stimulation in vivo.

Developmental checkpoints of the basophil/mast cell lineages in adult murine hematopoiesis.

Basophils and mast cells, which are selectively endowed with the high-affinity IgE receptor and mediate a range of adaptive and innate immune responses, have an unknown developmental relationship. Here, by evaluating the expression of the beta7 integrin, a molecule that is required for selective homing of mast cell progenitors (MCPs) to the periphery, we identified bipotent progenitors that are capable of differentiating into either cell type in the mouse spleen. These basophil/mast cell progenitors (BMCPs) gave rise to basophils and mast cells at the single-cell level and reconstituted both mucosal and connective tissue mast cells.

Identification of eosinophil lineage-committed progenitors in the murine bone marrow.

Eosinophil lineage-committed progenitors (EoPs) are phenotypically isolatable in the steady-state murine bone marrow. Purified granulocyte/monocyte progenitors (GMPs) gave rise to eosinophils as well as neutrophils and monocytes at the single cell level. Within the short-term culture of GMPs, the eosinophil potential was found exclusively in cells activating the transgenic reporter for GATA-1, a transcription factor capable of instructing eosinophil lineage commitment.

Distinctive and indispensable roles of PU.1 in maintenance of hematopoietic stem cells and their differentiation.

The PU.1 transcription factor is a key regulator of hematopoietic development, but its role at each hematopoietic stage remains unclear. In particular, the expression of PU.

Obligate role of anti-apoptotic MCL-1 in the survival of hematopoietic stem cells.

Apoptosis is important in controlling hematopoietic stem cell (HSC) numbers. However, the specific BCL-2 family member(s) that regulate HSC homeostasis are not precisely defined. We tested myeloid leukemia-1 (MCL-1) as an attractive candidate that is highly expressed in HSCs and regulated by growth factor signals.

Plasmacytoid dendritic cells activate lymphoid-specific genetic programs irrespective of their cellular origin.

The developmental origin of type I interferon (IFN)-producing plasmacytoid dendritic cells (PDCs) is controversial. In particular, the rearrangement of immunoglobulin heavy chain (IgH) genes in murine PDCs and the expression of pre-T cell receptor alpha (pTalpha) gene by human PDCs were proposed as evidence for their "lymphoid" origin. Here we demonstrate that PDCs capable of IFN production develop efficiently from both myeloid- and lymphoid-committed progenitors.

GATA-1 converts lymphoid and myelomonocytic progenitors into the megakaryocyte/erythrocyte lineages.

GATA-1 is an essential transcription factor for megakaryocyte and erythrocyte (MegE) development. Here we show that hematopoietic progenitors can be reprogrammed by the instructive action of GATA-1. Enforced expression of GATA-1 in hematopoietic stem cells led to loss of self-renewal activity and the exclusive generation of MegE lineages.