Synergic coordination of stem cells is required to induce a regenerative response in anthozoan cnidarians

AbstractLittle is known about the origin of the inductive signal that translates the amputation stress into a cooperative cellular response. By studying the process underlying the reformation of lost body parts in the anthozoan cnidarian Nematostella vectensis, we identified a regeneration-inducing structure that, via a tissue crosstalk, is responsible for the initiation of the repair program. We further revealed for the first time in anthozoan cnidarians, that fast and slow-cycling/quiescent stem cells respond to the amputation stress and actively participate in the reformation of lost body parts. Importantly, a synergic interaction of both stem cell populations is required to complete the regeneration process. Our findings suggest that the emergence/loss of structure complexity/compartmentalization influences the proprieties of tissue plasticity, changes the competence of a tissue to reprogram and, in the context of regeneration, the capacity of the tissue to emit or respond to a regeneration-inducing signal.

Download Full-text

Quiescent, Slow-Cycling Stem Cell Populations in Cancer: A Review of the Evidence and Discussion of Significance

Journal of Oncology ◽

10.1155/2011/396076 ◽

2011 ◽

Vol 2011 ◽

pp. 1-11 ◽

Cited By ~ 159

Author(s):

Nathan Moore ◽

Stephen Lyle

Keyword(s):

Cell Cycle ◽

Stem Cells ◽

Stem Cell ◽

Cancer Stem Cells ◽

Adult Stem Cells ◽

Cell Populations ◽

Proliferative Potential ◽

Cell Cycle Regulators ◽

Slow Cycling ◽

Stem Cell Populations

Long-lived cancer stem cells (CSCs) with indefinite proliferative potential have been identified in multiple epithelial cancer types. These cells are likely derived from transformed adult stem cells and are thought to share many characteristics with their parental population, including a quiescent slow-cycling phenotype. Various label-retaining techniques have been used to identify normal slow cycling adult stem cell populations and offer a unique methodology to functionally identify and isolate cancer stem cells. The quiescent nature of CSCs represents an inherent mechanism that at least partially explains chemotherapy resistance and recurrence in posttherapy cancer patients. Isolating and understanding the cell cycle regulatory mechanisms of quiescent cancer cells will be a key component to creation of future therapies that better target CSCs and totally eradicate tumors. Here we review the evidence for quiescent CSC populations and explore potential cell cycle regulators that may serve as future targets for elimination of these cells.

Download Full-text

Vaccination with MAGE-3 Protein Can Induce a Potent Immune Response in a Healthy Donor Which Can Be Adoptively Transferred Via Stem Cell Transplant (Tx) to a Multiple Myeloma (MM) Patient.

Blood ◽

10.1182/blood.v106.11.2197.2197 ◽

2005 ◽

Vol 106 (11) ◽

pp. 2197-2197 ◽

Cited By ~ 3

Author(s):

Sacha Gnjatic ◽

Susann Szmania ◽

Amberly Moreno ◽

M. Cottler-Fox ◽

John Shaughnessy ◽

...

Keyword(s):

Stem Cells ◽

Immune Response ◽

Humoral Immunity ◽

Healthy Donor ◽

Cellular Response ◽

Cross Reactivity ◽

Cell Transplant ◽

Cell Responses ◽

Humoral Responses ◽

First Time

Abstract A MAGE-3 positive, stage IIIA MM patient with a twin donor provided a unique opportunity to study if vaccination with MAGE-3 protein induces immune responses in the healthy twin, and if these responses can be adoptively transferred to the patient and expanded by booster vaccines. The patient was treated with MEL 200 tandem Tx (Tx1: auto, Tx2: syngeneic) and MAGE-3 recombinant protein in ASO2B adjuvant. The MAGE-3 negative, identical twin donor received 3 vaccines and was leukapheresed (LP1) one week after the 3rd vaccine to store vaccine-induced immune cells. Donor G-CSF mobilized stem cells (Tx2) were transfused fresh to the patient after MEL conditioning. Donor LP1 was transfused to the patient 21 days post Tx2 and followed by 8 booster vaccines. The donor continued vaccinations and LP2 was collected one week after the 8th vaccine and transfused to the patient who had received 4 of 8 planned booster vaccines. Ab responses to MAGE-3 and controls NY-ESO-1, LAGE-1, MAGE-1, MAGE-4, and p-53 were assessed by ELISA. MAGE-3 specific CD8+ T-cell responses to autologous EBV transformed cells pulsed with pooled 20-mer overlapping peptides from MAGE-3 were assessed by ELISPOT. Neither twin had pre-existing anti-MAGE-3 humoral immunity. The donor twin developed MAGE-3 ab up to 1/6400. The patient had a detectable anti-MAGE-3 titer post donor Tx2 (1/400) which was boosted by subsequent vaccinations (1/1600). After the transfer of LP2 and vaccines 5–8, the patient had MAGE-3 ab titers similar to those in the donor. There was low but significant cross-reactivity only to MAGE-4. A vaccine-induced CD8+ cellular response to a previously undescribed MAGE-3115–123, HLA-A68 restricted epitope was observed in the donor and patient. MAGE-3115–123 is in the same region as (but is distinct from) two other known HLA-A2 and -B40 epitopes. Further studies with recombinant MAGE-3 protein and tetramers are in progress to study if this epitope is indeed naturally processed and presented. The patient is in CR nearly 1 yr post Tx2. We show for the first time that vaccinating a healthy donor with a defined cancer-testis antigen can induce both cellular and humoral responses and that such responses can be transferred and expanded post Tx in the recipient. Close inspection of the ab curves shows that humoral immunity was transferred with the donor stem cells (Tx2) and expanded in the patient by further booster vaccines. We could not establish with certainty that LP1 and LP2 contributed further to transferring humoral or cellular immunity. It is hoped that this approach may be used to induce a specific anti-MM immune response after autologous or allogeneic Tx and reduce MM relapse. Figure Figure

Download Full-text

The Potential of Nail Mini-Organ Stem Cells in Skin, Nail and Digit Tips Regeneration

International Journal of Molecular Sciences ◽

10.3390/ijms22062864 ◽

2021 ◽

Vol 22 (6) ◽

pp. 2864

Author(s):

Anna Pulawska-Czub ◽

Tomasz D. Pieczonka ◽

Paula Mazurek ◽

Krzysztof Kobielak

Keyword(s):

Stem Cells ◽

Critical Role ◽

Nail Plate ◽

Molecular Characteristics ◽

Continuous Growth ◽

Physiological Conditions ◽

Morphogenetic Protein ◽

Slow Cycling ◽

Bifunctional Properties

Nails are highly keratinized skin appendages that exhibit continuous growth under physiological conditions and full regeneration upon removal. These mini-organs are maintained by two autonomous populations of skin stem cells. The fast-cycling, highly proliferative stem cells of the nail matrix (nail stem cells (NSCs)) predominantly replenish the nail plate. Furthermore, the slow-cycling population of the nail proximal fold (nail proximal fold stem cells (NPFSCs)) displays bifunctional properties by contributing to the peri-nail epidermis under the normal homeostasis and the nail structure upon injury. Here, we discuss nail mini-organ stem cells’ location and their role in skin and nail homeostasis and regeneration, emphasizing their importance to orchestrate the whole digit tip regeneration. Such endogenous regeneration capabilities are observed in rodents and primates. However, they are limited to the region adjacent to the nail’s proximal area, indicating the crucial role of nail mini-organ stem cells in digit restoration. Further, we explore the molecular characteristics of nail mini-organ stem cells and the critical role of the bone morphogenetic protein (BMP) and Wnt signaling pathways in homeostatic nail growth and digit restoration. Finally, we investigate the latest accomplishments in stimulating regenerative responses in regeneration-incompetent injuries. These pioneer results might open up new opportunities to overcome amputated mammalian digits and limbs’ regenerative failures in the future.

Download Full-text

Direct observation of a coil-to-helix contraction triggered by vinculin binding to talin

Science Advances ◽

10.1126/sciadv.aaz4707 ◽

2020 ◽

Vol 6 (21) ◽

pp. eaaz4707 ◽

Cited By ~ 7

Author(s):

Rafael Tapia-Rojo ◽

Alvaro Alonso-Caballero ◽

Julio M. Fernandez

Keyword(s):

Focal Adhesions ◽

Interaction Force ◽

Magnetic Tweezers ◽

Feedback Mechanism ◽

Force Transmission ◽

Mechanical Coupling ◽

Negative Feedback Mechanism ◽

The Reformation ◽

Energy Penalty ◽

First Time

Vinculin binds unfolded talin domains in focal adhesions, which recruits actin filaments to reinforce the mechanical coupling of this organelle. However, it remains unknown how this interaction is regulated and its impact on the force transmission properties of this mechanotransduction pathway. Here, we use magnetic tweezers to measure the interaction between vinculin head and the talin R3 domain under physiological forces. For the first time, we resolve individual binding events as a short contraction of the unfolded talin polypeptide caused by the reformation of the vinculin-binding site helices, which dictates a biphasic mechanism that regulates this interaction. Force favors vinculin binding by unfolding talin and exposing the vinculin-binding sites; however, the coil-to-helix contraction introduces an energy penalty that increases with force, defining an optimal binding regime. This mechanism implies that the talin-vinculin-actin association could operate as a negative feedback mechanism to stabilize force on focal adhesions.

Download Full-text

Nanoliposomal Cercodemasoide A and Its Improved Activities Against NTERA-2 Cancer Stem Cells

Natural Product Communications ◽

10.1177/1934578x20982108 ◽

2020 ◽

Vol 15 (12) ◽

pp. 1934578X2098210

Author(s):

Nguyen Thi Nga ◽

Do Thi Phuong ◽

Nguyen Thi Cuc ◽

Trieu Ha Phuong ◽

Pham Thi Mai Huong ◽

...

Keyword(s):

Stem Cells ◽

Cancer Stem Cells ◽

Drug Carrier ◽

Free Form ◽

Cancer Therapies ◽

3 Dimensional ◽

Novel Target ◽

Average Size ◽

Biopharmaceutical Properties ◽

First Time

Recently, saponins derived from marine sources have received much attention because of their promising bioactivities, such as anticancer, anti-angiogenesis, and anti-inflammation. In particular, a triterpene saponin from the sea cucumber Cercodemas anceps Selenka, cercodemasoide A (CAN1), showed potent cytotoxicity against various cancer cell lines. Recent evidence has indicated that cancer stem cells (CSCs) could be a novel target for efficient cancer therapies. In order to improve the biopharmaceutical properties of CAN1, the compound was loaded into nanoliposomes as an ideal drug carrier. CAN1 was successfully incorporated into nanoliposomes as small unilamellar liposome vesicles with an average size of 73.39 ± 1.57 nm, zeta potential of −0.299 ± 0.046 mV, polydispersity index of 0.336 ± 0.038, and with an encapsulation efficiency of up to 62.9%. For the first time, CAN1 and its nanoliposomal forms have been shown to have a promising cytotoxic activity against NTERA-2 CSCs, with half-maximal inhibitory concentration (IC50) =1.03 ± 0.04 and 0.41 ± 0.03 µM, respectively. The CAN1 nanoliposomes also presented significantly improved activities in suppressing the growth of NTERA-2 3-dimensional tumorspheres (IC50 = 1.71 ± 0.06 µM) in comparison with the free form ( P < .05). The anti-CSC effects of CAN1 nanoliposomes on NTERA-2 cells were due to their apoptotic induction through enhancing caspase-3 activity (more than 2-fold) and arresting the cell cycle at the S phase ( P < .05). The obtained CAN1-encapsulated nanoliposomes suggest valuable applications in CSC-targeting treatment for more efficient clinical therapy.

Download Full-text

Autophagy augments the self-renewal of lung cancer stem cells by the degradation of ubiquitinated p53

Cell Death and Disease ◽

10.1038/s41419-021-03392-6 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Jianyu Wang ◽

Doudou Liu ◽

Zhiwei Sun ◽

Ting Ye ◽

Jingyuan Li ◽

...

Keyword(s):

Lung Cancer ◽

Stem Cells ◽

Cancer Stem Cells ◽

Cell Lines ◽

Human Cancer ◽

Suppressor Activity ◽

Self Renewal ◽

Tumor Suppressor Activity ◽

Lung Cancer Stem Cells ◽

First Time

AbstractIt has been postulated that cancer stem cells (CSCs) are involved in all aspects of human cancer, although the mechanisms governing the regulation of CSC self-renewal in the cancer state remain poorly defined. In the literature, both the pro- and anti-oncogenic activities of autophagy have been demonstrated and are context-dependent. Mounting evidence has shown augmentation of CSC stemness by autophagy, yet mechanistic characterization and understanding are lacking. In the present study, by generating stable human lung CSC cell lines with the wild-type TP53 (A549), as well as cell lines in which TP53 was deleted (H1229), we show, for the first time, that autophagy augments the stemness of lung CSCs by degrading ubiquitinated p53. Furthermore, Zeb1 is required for TP53 regulation of CSC self-renewal. Moreover, TCGA data mining and analysis show that Atg5 and Zeb1 are poor prognostic markers of lung cancer. In summary, this study has elucidated a new CSC-based mechanism underlying the oncogenic activity of autophagy and the tumor suppressor activity of p53 in cancer, i.e., CSCs can exploit the autophagy-p53-Zeb1 axis for self-renewal, oncogenesis, and progression.

Download Full-text

Refusing to Kiss the Slipper

10.1093/oso/9780197566954.001.0001 ◽

2021 ◽

Author(s):

Michael W. Bruening

Keyword(s):

Religious Authority ◽

Reform Strategies ◽

The Reformation ◽

French Speaking ◽

Traditional Assumption ◽

Open Discussion ◽

First Time ◽

The Way

Refusing to Kiss the Slipper re-examines the Reformation in francophone Europe, presenting for the first time the perspective of John Calvin’s evangelical enemies. This book brings together a cast of Calvin’s opponents from various French-speaking territories to show that opposition to Calvinism was stronger and better organized than has ever before been recognized. It examines individual opponents, such as Pierre Caroli, Jerome Bolsec, Sebastian Castellio, Charles Du Moulin, and Jean Morély, but more importantly, it explores the anti-Calvinist networks that developed around such individuals. Each group had its own origins and agenda, but all agreed that Calvin’s claim to absolute religious authority too closely echoed the religious sovereignty of the pope. These oft-neglected opponents refused to offer such obeisance—to kiss the papal slipper—arguing instead for open discussion of controversial doctrines. This book also shows that the challenge posed by these groups shaped the way the Calvinists themselves developed their reform strategies. The book demonstrates that the breadth and strength of the anti-Calvinist networks requires us to abandon the traditional assumption that Huguenots and other francophone Protestants were universally Calvinist.

Download Full-text

Regrow or Repair: An Update on Potential Regenerative Therapies for the Kidney

Journal of the American Society of Nephrology ◽

10.1681/asn.2021081073 ◽

2021 ◽

pp. ASN.2021081073

Author(s):

Melissa Little ◽

Benjamin Humphreys

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Kidney Development ◽

Transcriptional Analysis ◽

Cell Recruitment ◽

Renal Stem Cells ◽

Induced Pluripotent ◽

Stem Cell Populations ◽

A Site ◽

Regenerative Therapies

Fifteen years ago, this journal published a review outlining future options for regenerating the kidney. At that time, stem cell populations were being identified in multiple tissues, the concept of stem cell recruitment to a site of injury was of great interest, and the possibility of postnatal renal stem cells was growing in momentum. Since that time, we have seen the advent of human induced pluripotent stem cells, substantial advances in our capacity to both sequence and edit the genome, global and spatial transcriptional analysis down to the single-cell level, and a pandemic that has challenged our delivery of health care to all. This article will look back over this period of time to see how our view of kidney development, disease, repair, and regeneration has changed and envision a future for kidney regeneration and repair over the next 15 years.

Download Full-text

Regulation of ion transport by pH and [HCO3−] in isolated gills of the crab Neohelice (Chasmagnathus) granulata

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00516.2007 ◽

2008 ◽

Vol 294 (3) ◽

pp. R1033-R1043 ◽

Cited By ~ 15

Author(s):

Martin Tresguerres ◽

Scott K. Parks ◽

Sebastian E. Sabatini ◽

Greg G. Goss ◽

Carlos M. Luquet

Keyword(s):

Carbonic Anhydrase ◽

Ion Transport ◽

Acid Secretion ◽

Cellular Response ◽

Low Ph ◽

Potential Difference ◽

Anion Exchangers ◽

Transepithelial Potential Difference ◽

Chasmagnathus Granulata ◽

First Time

Posterior isolated gills of Neohelice ( Chasmagnathus) granulatus were symmetrically perfused with hemolymph-like saline of varying [HCO3−] and pH. Elevating [HCO3−] in the saline from 2.5 to 12.5 mmol/l (pH 7.75 in both cases) induced a significant increase in the transepithelial potential difference ( Vte), a measure of ion transport. The elevation in [HCO3−] also induced a switch from acid secretion (−43.7 ± 22.5 μequiv·kg−1·h−1) in controls to base secretion (84.7 ± 14.4 μequiv·kg−1·h−1). The HCO3−-induced Vte increase was inhibited by basolateral acetazolamide (200 μmol/l), amiloride (1 mmol/l), and ouabain (5 mmol/l) but not by bafilomycin (100 nmol/l). The Vte response to HCO3− did not take place in Cl−-free conditions; however, it was unaffected by apical SITS (2 mmol/l) or DIDS (1 mmol/l). A decrease in pH from 7.75 to 7.45 pH units in the perfusate also induced a significant increase in Vte, which was matched by a net increase in acid secretion of 67.8 ± 18.4 μequiv kg−1 h−1. This stimulation was sensitive to basolateral acetazolamide, bafilomycin, DIDS, and Na+-free conditions, but it still took place in Cl−-free saline. Therefore, the cellular response to low pH is different from the HCO3−-stimulated response. We also report V-H+-ATPase- and Na+-K+-ATPase-like immunoreactivity in gill sections for the first time in this crab. Our results suggest that carbonic anhydrase (CA), basolateral Na+/H+ exchangers and Na+-K+-ATPase and apical anion exchangers participate in the HCO3−-stimulated response, while CA, apical V-H+-ATPase and basolateral HCO3−-dependent cotransporters mediate the response to low pH.

Download Full-text