scholarly journals Reciprocal interaction between mesenchymal stem cells and transit amplifying cells regulates tissue homeostasis

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Junjun Jing ◽  
Jifan Feng ◽  
Jingyuan Li ◽  
Hu Zhao ◽  
Thach-Vu Ho ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Wnt Signaling ◽  
Adult Stem Cells ◽  
Cell Types ◽  
Tissue Homeostasis ◽  
Canonical Wnt Signaling ◽  
Multiple Organs ◽  
Canonical Wnt

Interaction between adult stem cells and their progeny is critical for tissue homeostasis and regeneration. In multiple organs, mesenchymal stem cells (MSCs) give rise to transit amplifying cells (TACs), which then differentiate into different cell types. However, whether and how MSCs interact with TACs remains unknown. Using the adult mouse incisor as a model, we present in vivo evidence that TACs and MSCs have distinct genetic programs and engage in reciprocal signaling cross talk to maintain tissue homeostasis. Specifically, an IGF-WNT signaling cascade is involved in the feedforward from MSCs to TACs. TACs are regulated by tissue-autonomous canonical WNT signaling and can feedback to MSCs and regulate MSC maintenance via Wnt5a/Ror2-mediated non-canonical WNT signaling. Collectively, these findings highlight the importance of coordinated bidirectional signaling interaction between MSCs and TACs in instructing mesenchymal tissue homeostasis, and the mechanisms identified here have important implications for MSC–TAC interaction in other organs.

scholarly journals Inhibition versus activation of canonical Wnt-signaling, to promote chondrogenic differentiation of Mesenchymal Stem Cells. A review.

2021 ◽  
Author(s):  
Nikitas P. Schizas ◽  
Christos Zafeiris ◽  
Anna-Aikaterini Neri ◽  
Panagiotis P. Anastasopoulos ◽  
Nikolaos A. Papaioannou ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Wnt Signaling ◽  
Chondrogenic Differentiation ◽  
Canonical Wnt Signaling ◽  
Canonical Wnt

scholarly journals Icariin Regulates the Bidirectional Differentiation of Bone Marrow Mesenchymal Stem Cells through Canonical Wnt Signaling Pathway

2017 ◽  
Vol 2017 ◽  
pp. 1-12 ◽  
Author(s):  
Jun-ming Huang ◽  
Yuan Bao ◽  
Wei Xiang ◽  
Xing-zhi Jing ◽  
Jia-chao Guo ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Western Blot ◽  
Wnt Signaling ◽  
Signaling Pathway ◽  
Wnt Signaling Pathway ◽  
Canonical Wnt Signaling ◽  
Marrow Mesenchymal Stem Cells ◽  
Canonical Wnt

Fat infiltration within the bone marrow is easily observed in some postmenopausal women. Those fats are mainly derived from bone marrow mesenchymal stem cells (BMMSCs). The increment of adipocytes derived from BMMSCs leads to decreased osteoblasts derived from BMMSCs, so the bidirectional differentiation of BMMSCs significantly contributes to osteoporosis. Icariin is the main extractive of Herba Epimedii which is widely used in traditional Chinese medicine. In this experiment, we investigated the effect of icariin on the bidirectional differentiation of BMMSCs through quantitative real-time PCR, immunofluorescence, western blot, and tissue sections in vitro and in vivo. We found that icariin obviously promotes osteogenesis and inhibits adipogenesis through detecting staining and gene expression. Micro-CT analysis showed that icariin treatment alleviated the loss of cancellous bone of the distal femur in ovariectomized (OVX) mice. H&E staining analysis showed that icariin-treated OVX mice obtained higher bone mass and fewer bone marrow lipid droplets than OVX mice. Western blot and immunofluorescence showed that icariin regulates the bidirectional differentiation of BMMSCs via canonical Wnt signaling. This study demonstrates that icariin exerts its antiosteoporotic effect by regulating the bidirectional differentiation of BMMSCs through the canonical Wnt signaling pathway.

Differential Dependence On Wnt Signaling Allows Chemical Mediated Eradication of Human Acute Leukemia without Affecting Normal Blood Stem Cells

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 3278-3278
Author(s):  
Ruth M. Risueño ◽  
Eva Szabo ◽  
Uyen Maria Dang ◽  
Marilyne Levadoux-Martin ◽  
Jae-Uk Chung ◽  
...  
Keyword(s):  
Stem Cells ◽  
Wnt Signaling ◽  
Small Molecule ◽  
Ex Vivo ◽  
Parent Compound ◽  
Canonical Wnt Signaling ◽  
Self Renewal ◽  
Hematopoietic Stem ◽  
Canonical Wnt

Abstract Abstract 3278 Specific targets of signaling pathways that control self-renewal and survival of acute myeloid leukemic stem cells (LSCs) vs. normal hematopoietic stem cells (HSCs) are largely unknown. Here, using a small molecule (CWP232228) derived from a parent compound that inhibits Wnt/TCF targets, we demonstrate reduction of primary human AML-blast growth and clonogenic capacity ex vivo, without effects on normal hematopoietic progenitors. Upon establishment of AML or normal hematopoiesis in immune-deficient recipients, in vivo administration of CWP232228 reduced leukemic disease and abolished LSC self-renewal, with no effect on normal HSC function. In vivo gene profiling and ex vivo molecular studies revealed that CWP232228 induces apoptosis and differentiation of AML-blasts via inhibition of Wnt/b-catenin signaling and activation of non-canonical Wnt signaling which phenocopies the effects of this small molecule. Our study reveals an in vivo differential dependence of AML on canonical vs. non-canonical Wnt signaling that allows therapeutic targeting of LSCs whilst sparing normal HSCs. Disclosures: Chung: Choongwae Pharma Corporation: Employment.

scholarly journals Bortezomib induces osteoblast differentiation via Wnt-independent activation of β-catenin/TCF signaling

Blood ◽  
2009 ◽  
Vol 113 (18) ◽  
pp. 4319-4330 ◽  
Author(s):  
Ya-Wei Qiang ◽  
Bo Hu ◽  
Yu Chen ◽  
Ying Zhong ◽  
Bingyin Shi ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Wnt Signaling ◽  
Nuclear Translocation ◽  
Dominant Negative ◽  
Calcium Deposition ◽  
Canonical Wnt Signaling ◽  
Matrix Mineralization ◽  
Canonical Wnt

Abstract Inhibition of Wnt/β-catenin/T-cell factor (TCF) signaling induces proliferation of mesenchymal stem cells and/or suppresses their differentiation into osteoblasts (OBs). Osteolysis in multiple myeloma (MM) is related to the suppression of canonical Wnt signaling caused by DKK1, a soluble inhibitor of this pathway secreted by MM cells. Bortezomib (Bzb) can induce OB differentiation in vitro and in vivo and its anti-MM efficacy linked to bone anabolic effects. However, the molecular basis of the action of Bzb on bone is not completely understood. In the present study, we show that Bzb promotes matrix mineralization and calcium deposition by osteoprogenitor cells and primary mesenchymal stem cells via Wnt-independent activation of β-catenin/TCF signaling. Using affinity pull-down assays with immunoblotting and immunofluorescence, we found that Bzb induced stabilization of β-catenin. Nuclear translocation of stabilized β-catenin was associated with β-catenin/TCF transcriptional activity that was independent of the effects of Wnt ligand-receptor-induced signaling or GSK3β activation. Blocking the activation of β-catenin/TCF signaling by dominant negative TCF attenuated Bzb-induced matrix mineralization. These results provide evidence that Bzb induces OB differentiation via Wnt-independent activation of β-catenin/TCF pathway and suggest that proteasome inhibition therapy in MM may function in part by subverting tumor-induced suppression of canonical Wnt signaling in the bone microenvironment.

scholarly journals A Wnt5a-Cdc42 axis controls aging and rejuvenation of hair-follicle stem cells

2020 ◽  
Author(s):  
Rajiv L Tiwari ◽  
Pratibha Mishra ◽  
Nicola Martin ◽  
Nikhil Oommen George ◽  
Vadim Sakk ◽  
...  
Keyword(s):  
Stem Cells ◽  
Wnt Signaling ◽  
Hair Follicle ◽  
Canonical Wnt Signaling ◽  
Hair Regeneration ◽  
Hair Follicle Stem Cells ◽  
Elevated Activity ◽  
Canonical Wnt ◽  
Follicle Stem Cells

SummaryNormal hair growth occurs in cycles, comprising growth (anagen), cessation (catagen) and rest (telogen). Upon aging, the initiation of anagen is significantly delayed, which results in impaired hair regeneration. Hair regeneration is driven by hair follicle stem cells (HFSCs). We show here that aged HFSCs present with a decrease in canonical Wnt signaling and a shift towards non-canonical Wnt5a driven signaling which antagonizes canonical Wnt signaling. Elevated expression of Wnt5a in HFSCs upon aging results in elevated activity of the small RhoGTPase Cdc42 as well as a change in the spatial distribution of Cdc42 within HFSCs. Treatment of aged HFSC with a specific pharmacological inhibitor of Cdc42 activity termed CASIN to suppress the aging-associated elevated activity of Cdc42 restored canonical Wnt signaling in aged HFSCs. Treatment of aged mice in vivo with CASIN induced anagen onset and increased the percentage of anagen skin areas. Aging-associated functional deficits of HFSCs are at least in part intrinsic to HFSCs and can be restored by rational pharmacological approaches.

scholarly journals A Wnt5a-Cdc42 axis controls aging and rejuvenation of hair-follicle stem cells

2020 ◽  
Author(s):  
Rajiv Tiwari ◽  
Pratibha Mishra ◽  
Nicola Martin ◽  
Nikhil George ◽  
Vadim Sakk ◽  
...  
Keyword(s):  
Stem Cells ◽  
Wnt Signaling ◽  
Hair Follicle ◽  
Canonical Wnt Signaling ◽  
Hair Regeneration ◽  
Hair Follicle Stem Cells ◽  
Elevated Activity ◽  
Canonical Wnt ◽  
Follicle Stem Cells

Abstract Normal hair growth occurs in cycles, comprising growth (anagen), cessation (catagen) and rest (telogen). Upon aging, the initiation of anagen is significantly delayed, which results in impaired hair regeneration. Hair regeneration is driven by hair follicle stem cells (HFSCs). We show here that aged HFSCs present with a decrease in canonical Wnt signaling and a shift towards non-canonical Wnt5a driven signaling which antagonizes canonical Wnt signaling. Elevated expression of Wnt5a in HFSCs upon aging results in elevated activity of the small RhoGTPase Cdc42 as well as a change in the spatial distribution of Cdc42 within HFSCs. Treatment of aged HFSC with a specific pharmacological inhibitor of Cdc42 activity termed CASIN to suppress the aging-associated elevated activity of Cdc42 restored canonical Wnt signaling in aged HFSCs. Treatment of aged mice in vivo with CASIN induced anagen onset and increased the percentage of anagen skin areas. Aging-associated functional deficits of HFSCs are at least in part intrinsic to HFSCs and can be restored by rational pharmacological approaches.

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