scholarly journals Coupling of Hedgehog and Hippo pathways promotes stem cell maintenance by stimulating proliferation

2014 ◽  
Vol 205 (3) ◽  
pp. 325-338 ◽  
Author(s):  
Jianhua Huang ◽  
Daniel Kalderon

It is essential to define the mechanisms by which external signals regulate adult stem cell numbers, stem cell maintenance, and stem cell proliferation to guide regenerative stem cell therapies and to understand better how cancers originate in stem cells. In this paper, we show that Hedgehog (Hh) signaling in Drosophila melanogaster ovarian follicle stem cells (FSCs) induces the activity of Yorkie (Yki), the transcriptional coactivator of the Hippo pathway, by inducing yki transcription. Moreover, both Hh signaling and Yki positively regulate the rate of FSC proliferation, both are essential for FSC maintenance, and both promote increased FSC longevity and FSC duplication when in excess. We also found that responses to activated Yki depend on Cyclin E induction while responses to excess Hh signaling depend on Yki induction, and excess Yki can compensate for defective Hh signaling. These causal connections provide the most rigorous evidence to date that a niche signal can promote stem cell maintenance principally by stimulating stem cell proliferation.

2009 ◽  
Vol 5 (1) ◽  
pp. 64-75 ◽  
Author(s):  
Xiaohua Su ◽  
Maryline Paris ◽  
Young Jin Gi ◽  
Kenneth Y. Tsai ◽  
Min Soon Cho ◽  
...  

2020 ◽  
Vol 31 (14) ◽  
pp. 1538-1549
Author(s):  
Fan Zhang ◽  
Mehdi Pirooznia ◽  
Hong Xu

Deficiencies in electron transport chain complexes increase the activity of FOXO transcription factor in Drosophila midgut stem cells, which impairs stem cell proliferation and enterocyte specification.


Blood ◽  
1993 ◽  
Vol 81 (2) ◽  
pp. 365-372 ◽  
Author(s):  
JP Wineman ◽  
S Nishikawa ◽  
CE Muller-Sieburg

We show here that mouse pluripotent hematopoietic stem cells can be maintained in vitro on stroma for at least 3 weeks at levels close to those found in bone marrow. The extent of stem cell maintenance is affected by the nature of the stromal cells. The stromal cell line S17 supported stem cells significantly better than heterogeneous, primary stromal layers or the stromal cell line Strofl-1. Stem cells cultured on S17 repopulated all hematopoietic lineages in marrow-ablated hosts for at least 10 months, indicating that this culture system maintained primitive stem cells with extensive proliferative capacity. Furthermore, we demonstrate that, while pluripotent stem cells express c-kit, this receptor appears to play only a minor role in stem cell maintenance in vitro. The addition of an antibody that blocks the interaction of c-kit with its ligand essentially abrogated myelopoiesis in cultures. However, the level of stem cells in antibody-treated cultures was similar to that found in untreated cultures. Thus, it seems likely that the maintenance of primitive stem cells in vitro depends on yet unidentified stromal cell-derived factor(s).


INDIAN DRUGS ◽  
2017 ◽  
Vol 54 (02) ◽  
pp. 73-75
Author(s):  
S. Priya ◽  

Herbal stem cell therapy promotes endogenous stem cell proliferation and differentiation and is ued in the treatment of various human diseases. At present, recommendations are warranted to support the consumption of foods rich in bioactive components. Stem cells and progenitor cells from organs form the basis for well-being of the mammalian system. Analysis based on these cultured cells would form a viable alternative to stem cell transplantation, and would facilitate to design approaches that stimulate endogenous stem cells through diet to promote healing and regeneration. In the present study, synergistic activity of selected herbs such as Phyllanthus amarus, Myristica fragrans, Ocimum sanctum and Withania somnifera were analysed for their stem cell proliferation enhancing activity using goat bone marrow derived stem cells.


2019 ◽  
Author(s):  
Norihiko Saito ◽  
Nozomi Hirai ◽  
Kazuya Aoki ◽  
Satoshi Fujita ◽  
Haruo Nakayama ◽  
...  

2019 ◽  
Vol 51 (11) ◽  
pp. 1-12 ◽  
Author(s):  
June Sung Bae ◽  
Sun Mi Kim ◽  
Yoon Jeon ◽  
Juyeon Sim ◽  
Ji Yun Jang ◽  
...  

AbstractThe Hippo pathway plays a crucial role in cell proliferation and apoptosis and can regulate stem cell maintenance and embryonic development. MOB kinase activators 1A and 1B (Mob1a/b) are key components of the Hippo pathway, whose homozygous deletion in mice causes early embryonic lethality at the preimplantation stage. To investigate the role of Mob1a/b in stem cell maintenance and differentiation, an embryonic stem cell (ESC) clone in which Mob1a/b could be conditionally depleted was generated and characterized. Although Mob1a/b depletion did not affect the stemness or proliferation of mouse ESCs, this depletion caused defects in differentiation into the three germ layers. Yap knockdown rescued the in vitro and in vivo defects in differentiation caused by Mob1a/b depletion, suggesting that differentiation defects caused by Mob1a/b depletion were Yap-dependent. In teratoma experiments, Yap knockdown in Mob1a/b-depleted ESCs partially restored defects in differentiation, indicating that hyperactivation of Taz, another effector of the Hippo pathway, inhibited differentiation into the three germ layers. Taken together, these results suggest that Mob1a/b or Hippo signaling plays a critical role in the differentiation of mouse ESCs into the three germ layers, which is dependent on Yap. These close relationship of the Hippo pathway with the differentiation of stem cells supports its potential as a therapeutic target in regenerative medicine.


PLoS Genetics ◽  
2019 ◽  
Vol 15 (6) ◽  
pp. e1008187 ◽  
Author(s):  
Benjamin Angulo ◽  
Shrividhya Srinivasan ◽  
Benjamin J. Bolival ◽  
Gonzalo H. Olivares ◽  
Allyson C. Spence ◽  
...  

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