Inducible Fli-1 gene deletion in adult mice modifies several myeloid lineage commitment decisions and accelerates proliferation arrest and terminal erythrocytic differentiation

Blood ◽  
2010 ◽  
Vol 116 (23) ◽  
pp. 4795-4805 ◽  
Author(s):  
Joëlle Starck ◽  
Michèle Weiss-Gayet ◽  
Colette Gonnet ◽  
Boris Guyot ◽  
Jean-Michel Vicat ◽  
...  
Keyword(s):  
Cell Sorting ◽  
Gene Deletion ◽  
Liquid Cultures ◽  
Drastic Decrease ◽  
Differentiated Cells ◽  
Adult Mice ◽  
Myeloid Progenitor ◽  
Ets Transcription Factor ◽  
Late Stages

Abstract This study investigated the role of the ETS transcription factor Fli-1 in adult myelopoiesis using new transgenic mice allowing inducible Fli-1 gene deletion. Fli-1 deletion in adult induced mild thrombocytopenia associated with a drastic decrease in large mature megakaryocytes number. Bone marrow bipotent megakaryocytic-erythrocytic progenitors (MEPs) increased by 50% without increase in erythrocytic and megakaryocytic common myeloid progenitor progeny, suggesting increased production from upstream stem cells. These MEPs were almost unable to generate pure colonies containing large mature megakaryocytes, but generated the same total number of colonies mainly identifiable as erythroid colonies containing a reduced number of more differentiated cells. Cytological and fluorescence-activated cell sorting analyses of MEP progeny in semisolid and liquid cultures confirmed the drastic decrease in large mature megakaryocytes but revealed a surprisingly modest (50%) reduction of CD41-positive cells indicating the persistence of a megakaryocytic commitment potential. Symmetrical increase and decrease of monocytic and granulocytic progenitors were also observed in the progeny of purified granulocytic-monocytic progenitors and common myeloid progenitors. In summary, this study indicates that Fli-1 controls several lineages commitment decisions at the stem cell, MEP, and granulocytic-monocytic progenitor levels, stimulates the proliferation of committed erythrocytic progenitors at the expense of their differentiation, and is a major regulator of late stages of megakaryocytic differentiation.

Activation of Notch1 Signaling Suppresses Granulocytic Differentiation and Maintains a Part of Myeloid Progenitor Cells At the Immature Stage

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 2375-2375
Author(s):  
Makoto Nakamura ◽  
Lizi Wu ◽  
Satoru Kojika ◽  
James D. Griffin ◽  
Kanji Sugita
Keyword(s):  
Notch Signaling ◽  
Immature Stage ◽  
The Other ◽  
Granulocytic Differentiation ◽  
Notch1 Signaling ◽  
Differentiated Cells ◽  
Myeloid Progenitor ◽  
Myeloid Progenitor Cells ◽  
The Difference

Abstract Abstract 2375 The Notch signaling pathway is evolutionally conserved and has crucial roles in the control of fate decision and differentiation in numerous cell types. Although Notch1 is continuously expressed in differentiation myeloid cells, the role of Notch1 signaling in regulating differentiation remains controversial. Here, we enhanced and/or suppressed Notch signaling in myeloblasts and then determined the effects of Notch signaling modulation on granulocytic differentiation. Specifically, we first transduced myeloblastic 32D and HL60 cells with retroviruses that express the intracellular domain of Notch1 (ICN1; pMSCV-ICN1-IRES-GFP) to activate Notch1 signaling, or alternatively expressed a dominant-negative form of Mastermind-like 1 (DNMAML1; pMSCV-DNMAML1-GFP) to inhibit Notch signaling. Then the transduced (GFP+) and untransduced (GFP-) cells were induced into granulocytic differentiation using G-CSF for 32D cells and ATRA for HL60 cells. The degree of granulocytic differentiation was then assessed by flow cytometric analysis of surface expression of CD11b, a marker of granulocytic lineage. We found that the percentage of differentiated cells (CD11bhigh for 32D and CD11b+ for HL60) in the ICN1 expressing (GFP+) group was significantly (p < 0.05) lower than that in the control (GFP-) group for most time-points that we examined, whereas the difference in the proportion of differentiated cells between DNMAML1 expressing (GFP+) and control (GFP-) groups was not statistically significant. These data suggest that forced activation of Notch1 signaling inhibits granulocytic differentiation, whereas endogenous Notch1 signaling appears not to have a major role in granulocytic maturation in these cell lines. Next, We further studied the role of Notch1 signaling in granulopoiesis by first activating Notch1 signaling in 32D cells by stable expression of exogenous ICN1 followed by Notch inhibition via DNMAML1 expression within the same cells. The subsequent four sub-populations of 32D cells termed as Vec/GFP (control), Vec/DNMAML1 (cells with endogenous Notch signaling blocked by DNMAML1, ICN1/GFP (cells with activating Notch1), and ICN1/DNMAML1 (cells with activating Notch1 followed by Notch signaling inhibition) were then cultured with G-CSF and evaluated for differentiation by CD11b staining. We found that on days 6 and 8 after the induction of differentiation, the proportion of differentiated (CD11bhigh) cells in ICN1/GFP was significantly (p < 0.05) lower than those in the other sub-populations, supporting that ICN1 inhibits granulocytic differentiation of 32D cells. On the other hand, the difference in the proportion of differentiated cells between the other 3 sub-populations was not statistically significant at any time-points, suggesting that DNMAML1 reverses the phenotype induced by activated Notch1 and that endogenous Notch1 signaling may have no effect on granulocytic maturation. Real-time RT-PCR analysis of cytoplasmic expression of myeloperoxidase (MPO) indicated that the MPO expression reached maximal level by day 2 in control (Vec/GFP) cells, the peak was delayed until day 5 in ICN1/GFP cells. The peak expression was observed on day 3 in both Vec/DNMAML1 and ICN1/DNMAML1 cells, indicating that ICN1 represses or delays granulocytic differentiation and that DNMAML1 partially neutralizes such a phenotype. Furthermore, morphological analysis, viable cell count, and cell cycle analysis revealed that a subset of ICN1/GFP cells remained myeloblastic with proliferative capacity after the induction of granulocytic differentiation, supporting the idea that ICN1 inhibits granulocytic differentiation. Our data indicate that Notch1 signaling activation suppresses granulocytic differentiation, and maintains a part of myeloid progenitor cells at the immature stage. Therefore, it suggests that aberrant Notch1 signaling could support the granulocytic transformation and the maintenance of the malignant phenotype. Disclosures: Griffin: Novartis Pharmaceuticals: Consultancy, Research Funding.

scholarly journals GABP transcription factor is required for myeloid differentiation, in part, through its control of Gfi-1 expression

Blood ◽  
2011 ◽  
Vol 118 (8) ◽  
pp. 2243-2253 ◽  
Author(s):  
Zhong-Fa Yang ◽  
Karen Drumea ◽  
James Cormier ◽  
Junling Wang ◽  
Xuejun Zhu ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Transcription Factor ◽  
Myeloid Cells ◽  
Myeloid Differentiation ◽  
Myeloid Progenitor ◽  
Abnormal Bone Marrow ◽  
Myeloid Progenitor Cells ◽  
Ets Domain ◽  
Ets Transcription Factor

Abstract GABP is an ets transcription factor that regulates genes that are required for myeloid differentiation. The tetrameric GABP complex includes GABPα, which binds DNA via its ets domain, and GABPβ, which contains the transcription activation domain. To examine the role of GABP in myeloid differentiation, we generated mice in which Gabpa can be conditionally deleted in hematopoietic tissues. Gabpa knockout mice rapidly lost myeloid cells, and residual myeloid cells were dysplastic and immunophenotypically abnormal. Bone marrow transplantation demonstrated that Gabpα null cells could not contribute to the myeloid compartment because of cell intrinsic defects. Disruption of Gabpa was associated with a marked reduction in myeloid progenitor cells, and Gabpα null myeloid cells express reduced levels of the transcriptional repressor, Gfi-1. Gabp bound and activated the Gfi1 promoter, and transduction of Gabpa knockout bone marrow with Gfi1 partially rescued defects in myeloid colony formation and myeloid differentiation. We conclude that Gabp is required for myeloid differentiation due, in part, to its regulation of the tran-scriptional repressor Gfi-1.

Loss of Runx1 Perturbs Adult Hematopoiesis and Is Associated with a Myeloproliferative Phenotype.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 227-227
Author(s):  
Joseph D. Growney ◽  
Hirokazu Shigematsu ◽  
Zhe Li ◽  
Benjamin H. Lee ◽  
Jennifer Adelsperger ◽  
...  
Keyword(s):  
Critical Role ◽  
Extramedullary Hematopoiesis ◽  
Loss Of Function ◽  
Hematopoietic Malignancies ◽  
Adult Mice ◽  
Specific Effects ◽  
Myeloid Progenitor ◽  
Blood Neutrophils ◽  
T Cell Maturation

Abstract Homozygous loss of function of Runx1 during murine development results in an embryonic lethal phenotype characterized by a complete lack of definitive hematopoiesis. In light of recent reports of disparate requirements for hematopoietic transcription factors during development as opposed to adult hematopoiesis, we employed a conditional gene targeting strategy to effect loss of Runx1 function in adult mice. In contrast with the critical role of Runx1 during development, Runx1 was not essential for hematopoiesis in the adult hematopoietic compartment, although there were a number of significant hematopoietic abnormalities observed. Runx1 excision had significant lineage specific effects on B- and T-cell maturation, as well as pronounced inhibition of common lymphocyte progenitor production. Runx1 excision also resulted in inefficient platelet production. Of note, Runx1 deficient mice developed a mild myeloproliferative phenotype characterized by an increase in peripheral blood neutrophils, an increase in myeloid progenitor populations, and extramedullary hematopoiesis comprised of maturing myeloid and erythroid elements. These findings indicate that Runx1 deficiency has markedly different consequences during development compared with adult hematopoiesis, and provides insights into the phenotypic manifestations of Runx1 deficiency in hematopoietic malignancies.

PTTG has a Dual Role of Promotion-Inhibition in the Development of Pituitary Adenomas

2019 ◽  
Vol 26 (11) ◽  
pp. 800-818
Author(s):  
Zujian Xiong ◽  
Xuejun Li ◽  
Qi Yang
Keyword(s):  
Cell Cycle ◽  
Pituitary Adenoma ◽  
Pituitary Adenomas ◽  
Cell Cycle Progression ◽  
Key Factors ◽  
Cycle Progression ◽  
Sister Chromatids ◽  
Regulation Of Cell Cycle ◽  
Late Stages

Pituitary Tumor Transforming Gene (PTTG) of human is known as a checkpoint gene in the middle and late stages of mitosis, and is also a proto-oncogene that promotes cell cycle progression. In the nucleus, PTTG works as securin in controlling the mid-term segregation of sister chromatids. Overexpression of PTTG, entering the nucleus with the help of PBF in pituitary adenomas, participates in the regulation of cell cycle, interferes with DNA repair, induces genetic instability, transactivates FGF-2 and VEGF and promotes angiogenesis and tumor invasion. Simultaneously, overexpression of PTTG induces tumor cell senescence through the DNA damage pathway, making pituitary adenoma possessing the potential self-limiting ability. To elucidate the mechanism of PTTG in the regulation of pituitary adenomas, we focus on both the positive and negative function of PTTG and find out key factors interacted with PTTG in pituitary adenomas. Furthermore, we discuss other possible mechanisms correlate with PTTG in pituitary adenoma initiation and development and the potential value of PTTG in clinical treatment.

scholarly journals Crayfish hemocytes develop along the granular cell lineage

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Fang Li ◽  
Zaichao Zheng ◽  
Hongyu Li ◽  
Rongrong Fu ◽  
Limei Xu ◽  
...  
Keyword(s):  
Developmental Stages ◽  
Cell Lineage ◽  
Granular Cell ◽  
Marker Genes ◽  
Hematopoietic Tissue ◽  
Differentiated Cells ◽  
Stage Of Development ◽  
Almost All ◽  
Relationship Of

AbstractDespite the central role of hemocytes in crustacean immunity, the process of hemocyte differentiation and maturation remains unclear. In some decapods, it has been proposed that the two main types of hemocytes, granular cells (GCs) and semigranular cells (SGCs), differentiate along separate lineages. However, our current findings challenge this model. By tracking newly produced hemocytes and transplanted cells, we demonstrate that almost all the circulating hemocytes of crayfish belong to the GC lineage. SGCs and GCs may represent hemocytes of different developmental stages rather than two types of fully differentiated cells. Hemocyte precursors produced by progenitor cells differentiate in the hematopoietic tissue (HPT) for 3 ~ 4 days. Immature hemocytes are released from HPT in the form of SGCs and take 1 ~ 3 months to mature in the circulation. GCs represent the terminal stage of development. They can survive for as long as 2 months. The changes in the expression pattern of marker genes during GC differentiation support our conclusions. Further analysis of hemocyte phagocytosis indicates the existence of functionally different subpopulations. These findings may reshape our understanding of crustacean hematopoiesis and may lead to reconsideration of the roles and relationship of circulating hemocytes.

scholarly journals Role of TRPM8 in switching between fever and hypothermia in adult mice during endotoxin-induced inflammation

2021 ◽  
pp. 100291
Author(s):  
Chinatsu Shiraki ◽  
Ririka Horikawa ◽  
Yuzuki Oe ◽  
Momoka Fujimoto ◽  
Kaho Okamoto ◽  
...  
Keyword(s):  
Adult Mice

scholarly journals Cardiac-specific, inducible ClC-3 gene deletion eliminates native volume-sensitive chloride channels and produces myocardial hypertrophy in adult mice

2010 ◽  
Vol 48 (1) ◽  
pp. 211-219 ◽  
Author(s):  
Dazhi Xiong ◽  
Nathanael S. Heyman ◽  
Judith Airey ◽  
Mi Zhang ◽  
Cherie A. Singer ◽  
...  
Keyword(s):  
Chloride Channels ◽  
Gene Deletion ◽  
Myocardial Hypertrophy ◽  
Adult Mice

Role of Light and Medium Composition on Growth and Valepotriate Contents in Valeriana glechomifolia Whole Plant Liquid Cultures

2006 ◽  
Vol 86 (2) ◽  
pp. 211-218 ◽  
Author(s):  
Denise Russowski ◽  
Natasha Maurmann ◽  
Sandra Beatriz Rech ◽  
Arthur Germano Fett-Neto
Keyword(s):  
Medium Composition ◽  
Liquid Cultures ◽  
Whole Plant ◽  
Role Of Light

The role of calcium in the increase in flocculence of yeast growing in the presence of copper

1965 ◽  
Vol 162 (989) ◽  
pp. 555-566 ◽  
Keyword(s):  
Liquid Medium ◽  
Cell Cultures ◽  
Chloride Solution ◽  
Liquid Copper ◽  
Acquired Resistance ◽  
Calcium Chloride Solution ◽  
Copper Resistance ◽  
Liquid Cultures ◽  
Selection Of

Growth in the presence of inhibitory concentrations of copper enhances the tendency of yeast to flocculate. Many yeasts will not flocculate unless calcium is included in the growth medium and Guinness strain 522 used in the present work required a relatively large amount. Single cell cultures may undergo variation during subculture, resulting in the production of a large number of variants (Chester 1963). The cells of these variants differ considerably in their ability to adhere together. Flocculation variants of strain 522 differed among themselves in the amount of calcium necessary for flocculation, the most flocculent variants requiring least calcium. Washed cells of the more flocculent yeasts removed more calcium from a calcium chloride solution than did those with lesser powers of adhesion. In a copper medium con­taining calcium the more flocculent variants replaced the less flocculent. Calcium protected cells from copper and the more flocculent variants enjoyed most protection. All variants acquired resistance to copper during growth in the copper medium. Despite the selection of the more flocculent yeasts during growth in liquid medium, their copper resistance was less than that of the less flocculent yeasts. When calcium was added to the liquid copper medium, cultures developed less resistance. It is concluded that the less flocculent cells, having less protection by calcium, were exposed to what was effectively a greater concentration of copper and therefore became more resistant. This greater resistance did not enable these cells to compete with the flocculent cells in liquid cultures.

A pro-nociceptive role of neuromedin U in adult mice

Pain ◽  
2003 ◽  
Vol 104 (3) ◽  
pp. 609-616 ◽  
Author(s):  
Chang Qing Cao ◽  
Xiao Hong Yu ◽  
Andy Dray ◽  
Angelo Filosa ◽  
Martin N Perkins
Keyword(s):  
Adult Mice
Sign in / Sign up

Export Citation Format

Share Document