scholarly journals Upregulation of the Drosophila Friend of GATA Gene u-shaped by JAK/STAT Signaling Maintains Lymph Gland Prohemocyte Potency

2009 ◽  
Vol 29 (22) ◽  
pp. 6086-6096 ◽  
Author(s):  
Hongjuan Gao ◽  
Xiaorong Wu ◽  
Nancy Fossett
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cell Fate ◽  
Stem Cell Niche ◽  
Lymph Gland ◽  
Hematopoietic Stem ◽  
Functional Conservation ◽  
Stat Signaling ◽  
Signaling Center ◽  
Cell Niche

ABSTRACT Studies using Drosophila melanogaster have contributed significantly to our understanding of the interaction between stem cells and their protective microenvironments or stem cell niches. During lymph gland hematopoiesis, the Drosophila posterior signaling center functions as a stem cell niche to maintain prohemocyte multipotency through Hedgehog and JAK/STAT signaling. In this study, we provide evidence that the Friend of GATA protein U-shaped is an important regulator of lymph gland prohemocyte potency and differentiation. U-shaped expression was determined to be upregulated in third-instar lymph gland prohemocytes and downregulated in a subpopulation of differentiating blood cells. Genetic analyses indicated that U-shaped maintains the prohemocyte population by blocking differentiation. In addition, activated STAT directly regulated ush expression as evidenced by results from loss- and gain-of-function studies and from analyses of the u-shaped hematopoietic cis-regulatory module. Collectively, these findings identify U-shaped as a downstream effector of the posterior signaling center, establishing a novel link between the stem cell niche and the intrinsic regulation of potency and differentiation. Given the functional conservation of Friend of GATA proteins and the role that GATA factors play during cell fate choice, these factors may regulate essential functions of vertebrate hematopoietic stem cells, including processing signals from the stem cell niche.

scholarly journals Hemmule: A Novel Structure with the Properties of the Stem Cell Niche

2020 ◽  
Vol 21 (2) ◽  
pp. 539
Author(s):  
Vitaly Vodyanoy ◽  
Oleg Pustovyy ◽  
Ludmila Globa ◽  
Randy J. Kulesza ◽  
Iryna Sorokulova
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Stem Cell ◽  
Stem Cell Niche ◽  
Hematopoietic Stem ◽  
Novel Structure ◽  
Hematopoietic Stem Cell Niches ◽  
Cell Niche ◽  
Stem Cell Niches ◽  
Rat Bone

Stem cells are nurtured and regulated by a specialized microenvironment known as stem cell niche. While the functions of the niches are well defined, their structure and location remain unclear. We have identified, in rat bone marrow, the seat of hematopoietic stem cells—extensively vascularized node-like compartments that fit the requirements for stem cell niche and that we called hemmules. Hemmules are round or oval structures of about one millimeter in diameter that are surrounded by a fine capsule, have afferent and efferent vessels, are filled with the extracellular matrix and mesenchymal, hematopoietic, endothelial stem cells, and contain cells of the megakaryocyte family, which are known for homeostatic quiescence and contribution to the bone marrow environment. We propose that hemmules are the long sought hematopoietic stem cell niches and that they are prototypical of stem cell niches in other organs.

scholarly journals Wnt-inhibitory factor 1 dysregulation of the bone marrow niche exhausts hematopoietic stem cells

Blood ◽  
2011 ◽  
Vol 118 (9) ◽  
pp. 2420-2429 ◽  
Author(s):  
Christoph Schaniel ◽  
Dario Sirabella ◽  
Jiajing Qiu ◽  
Xiaohong Niu ◽  
Ihor R. Lemischka ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Wnt Signaling ◽  
Cell Fate ◽  
Sonic Hedgehog ◽  
Hematopoietic Stem ◽  
Cell Fate Decisions ◽  
Cell Niche ◽  
Wnt Inhibitory Factor 1 ◽  
Stem Cell Pool

Abstract The role of Wnt signaling in hematopoietic stem cell fate decisions remains controversial. We elected to dysregulate Wnt signaling from the perspective of the stem cell niche by expressing the pan Wnt inhibitor, Wnt inhibitory factor 1 (Wif1), specifically in osteoblasts. Here we report that osteoblastic Wif1 overexpression disrupts stem cell quiescence, leading to a loss of self-renewal potential. Primitive stem and progenitor populations were more proliferative and elevated in bone marrow and spleen, manifesting an impaired ability to maintain a self-renewing stem cell pool. Exhaustion of the stem cell pool was apparent only in the context of systemic stress by chemotherapy or transplantation of wild-type stem cells into irradiated Wif1 hosts. Paradoxically this is mediated, at least in part, by an autocrine induction of canonical Wnt signaling in stem cells on sequestration of Wnts in the environment. Additional signaling pathways are dysregulated in this model, primarily activated Sonic Hedgehog signaling in stem cells as a result of Wif1-induced osteoblastic expression of Sonic Hedgehog. We find that dysregulation of the stem cell niche by overexpression of an individual component impacts other unanticipated regulatory pathways in a combinatorial manner, ultimately disrupting niche mediated stem cell fate decisions.

2011 - ENGINEERING A HEMATOPOIETIC STEM CELL NICHE BY REVITALIZING MESENCHYMAL STEM CELLS

2019 ◽  
Vol 76 ◽  
pp. S45
Author(s):  
Fumio Nakahara ◽  
Daniel Borger ◽  
Qiaozhi Wei ◽  
Sandra Pinho ◽  
Maria Maryanovich ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Stem Cell ◽  
Hematopoietic Stem Cell ◽  
Stem Cell Niche ◽  
Hematopoietic Stem ◽  
Hematopoietic Stem Cell Niche ◽  
Cell Niche

Does primary myelofibrosis involve a defective stem cell niche? From concept to evidence

Blood ◽  
2008 ◽  
Vol 112 (8) ◽  
pp. 3026-3035 ◽  
Author(s):  
Jean-Jacques Lataillade ◽  
Olivier Pierre-Louis ◽  
Hans Carl Hasselbalch ◽  
Georges Uzan ◽  
Claude Jasmin ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Cell Proliferation ◽  
Stem Cell ◽  
Hematopoietic Stem Cells ◽  
Stem Cell Niche ◽  
Primary Myelofibrosis ◽  
Hematopoietic Stem ◽  
Stem Cell Proliferation ◽  
Cell Niche

Abstract Primary myelofibrosis (PMF) is the rarest and the most severe Philadelphia-negative chronic myeloproliferative syndrome. By associating a clonal proliferation and a mobilization of hematopoietic stem cells from bone marrow to spleen with profound alterations of the stroma, PMF is a remarkable model in which deregulation of the stem cell niche is of utmost importance for the disease development. This paper reviews key data suggesting that an imbalance between endosteal and vascular niches participates in the development of clonal stem cell proliferation. Mechanisms by which bone marrow niches are altered with ensuing mobilization and homing of neoplastic hematopoietic stem cells in new or reinitialized niches in the spleen and liver are examined. Differences between signals delivered by both endosteal and vascular niches in the bone marrow and spleen of patients as well as the responsiveness of PMF stem cells to their specific signals are discussed. A proposal for integrating a potential role for the JAK2 mutation in their altered sensitivity is made. A better understanding of the cross talk between stem cells and their niche should imply new therapeutic strategies targeting not only intrinsic defects in stem cell signaling but also regulatory hematopoietic niche–derived signals and, consequently, stem cell proliferation.

scholarly journals Stem cell niche signals Wnt, Hedgehog, and Notch distinctively regulate Drosophila follicle precursor cell differentiation

2017 ◽  
Author(s):  
Wei Dai ◽  
Amy Peterson ◽  
Thomas Kenney ◽  
Denise J. Montell
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Progenitor Cells ◽  
Cell Fate ◽  
Stem Cell Niche ◽  
Adult Stem Cells ◽  
Cell Types ◽  
Wnt Signalling ◽  
Main Body ◽  
Cell Niche

AbstractAdult stem cells commonly give rise to transit-amplifying progenitors, whose progeny differentiate into distinct cell types. Signals within the stem cell niche maintain the undifferentiated state. However it is unclear whether or how niche signals might also coordinate fate decisions within the progenitor pool. Here we use quantitative microscopy to elucidate distinct roles for Wnt, Hedgehog (Hh), and Notch signalling in progenitor development in the Drosophila ovary. Follicle stem cells (FSCs) self-renew and produce precursors whose progeny adopt distinct polar, stalk, and main body cell fates. We show that a steep gradient of Wnt signalling maintains a multipotent state in proximally located progenitor cells by inhibiting expression of the cell fate determinant Eyes Absent (Eya). A shallower gradient of Hh signalling controls the proliferation to differentiation transition. The combination of Notch and Wnt signalling specifies polar cells. These findings reveal a mechanism by which multiple niche signals coordinate cell fate diversification of progenitor cells.

scholarly journals Hemmule: A Novel Structure with the Properties of the Stem Cell Niche

2019 ◽  
Author(s):  
Vitaly Vodyanoy ◽  
Oleg Pustovyy ◽  
Ludmila Globa ◽  
Randy J Kulesza Jr ◽  
Iryna Sorokulova
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Stem Cell ◽  
Stem Cell Niche ◽  
Hematopoietic Stem ◽  
Novel Structure ◽  
Hematopoietic Stem Cell Niches ◽  
Cell Niche ◽  
Stem Cell Niches ◽  
Rat Bone

Stem cells are nurtured and regulated by a specialized microenvironment known as stem cell niche. While the functions of the niches are well defined, their structure and location remain unclear. We have identified in rat bone marrow, the seat of hematopoietic stem cells, extensively vascularized node-like compartments that fit the requirements for stem cell niche and which we called hemmules. Hemmules are round or oval structures of about one millimeter in diameter that are surrounded by a fine capsule, have afferent and efferent vessels, are filled with the extracellular matrix and mesenchymal, hematopoietic, endothelial stem cells, and contain cells of the megakaryocyte family, which are known for homeostatic quiescence and contribution to the bone marrow environment. We propose that hemmules are the long sought hematopoietic stem cell niches and that they are prototypical of stem cell niches in other organs.

Donor cell leukemia: insight into cancer stem cells and the stem cell niche

Blood ◽  
2006 ◽  
Vol 109 (7) ◽  
pp. 2688-2692 ◽  
Author(s):  
Catherine M. Flynn ◽  
Dan S. Kaufman
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Stem Cell Niche ◽  
Donor Cell ◽  
Cell Leukemia ◽  
Hematopoietic Stem ◽  
Hematopoietic Microenvironment ◽  
Cell Niche ◽  
Insight Into ◽  
Donor Cell Leukemia

Abstract Donor cell leukemia (DCL) is a rare complication of hematopoietic cell transplantation (HCT). Its incidence has been reported between 0.12% and 5%, although the majority of cases are anecdotal. The mechanisms of leukemogenesis in DCL may be distinct from other types of leukemia. Possible causes of DCL include oncogenic alteration or premature aging of transplanted donor cells in an immunosuppressed person. Although many studies have recently better characterized leukemic stem cells, it is important to also consider that both intrinsic cell factors and external signals from the hematopoietic microenvironment govern the developmental fate of hematopoietic stem cells (HSCs). Therefore, in cases of DCL, alteration of the microenvironment after HCT may increase the likelihood that some progeny of normal HSCs become leukemic. This complex intercommunication between cells, growth factors, and cytokines in the hematopoietic microenvironment are critical to balance HSC self-renewal, proliferation, and differentiation. However, this homeostasis is likely perturbed in the development of DCL, allowing unique insight into the stimuli that regulate normal and potentially abnormal hematopoietic development. In this article, we discuss the possible pathogenesis of DCL, its association with stem cells, and its likely dependence on a less-supportive stem cell niche.

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