scholarly journals Integrin-alpha-6+ Stem Cells (ISCs) are responsible for whole body regeneration in an invertebrate chordate

2019 ◽  
Author(s):  
Susannah H. Kassmer ◽  
Adam Langenbacher ◽  
Anthony W. De Tomaso

AbstractColonial ascidians are the only chordates able to undergo whole body regeneration (WBR), during which entire new bodies can be regenerated from small fragments of blood vessels. Here, we show that during the early stages of WBR in Botrylloides diegensis, proliferation occurs only in small, blood-borne cells that express integrin-alpha-6 (IA6), pou3 and vasa. Ablation of proliferating cells using Mitomycin C (MMC) blocks WBR in vascular fragments, but can be rescued by injection of cycling cells isolated from an untreated individual. Using prospective isolation and limit dilution analyes, we found that FACS-isolated IA6+ stem cells (ISCs) could rescue WBR in MMC treated vascular fragments, even when injecting only a single cell. Lineage tracing using EdU-labeling further revealed that donor-derived ISCs directly give rise to regenerating tissues. Inhibitors of either Notch or canonical Wnt signaling block WBR and reduce proliferation of ISCs, indicating that these two pathways regulate ISC activation.

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Susannah H. Kassmer ◽  
Adam D. Langenbacher ◽  
Anthony W. De Tomaso

Abstract Colonial ascidians are the only chordates able to undergo whole body regeneration (WBR), during which entire new bodies can be regenerated from small fragments of blood vessels. Here, we show that during the early stages of WBR in Botrylloides diegensis, proliferation occurs only in small, blood-borne cells that express integrin-alpha-6 (IA6), pou3 and vasa. WBR cannot proceed when proliferating IA6+ cells are ablated with Mitomycin C, and injection of a single IA6+ Candidate stem cell can rescue WBR after ablation. Lineage tracing using EdU-labeling demonstrates that donor-derived IA6+ Candidate stem cells directly give rise to regenerating tissues. Inhibitors of either Notch or canonical Wnt signaling block WBR and reduce proliferation of IA6+ Candidate stem cells, indicating that these two pathways regulate their activation. In conclusion, we show that IA6+ Candidate stem cells are responsible for whole body regeneration and give rise to regenerating tissues.


2018 ◽  
Vol 115 (4) ◽  
pp. E610-E619 ◽  
Author(s):  
Onur Basak ◽  
Teresa G. Krieger ◽  
Mauro J. Muraro ◽  
Kay Wiebrands ◽  
Daniel E. Stange ◽  
...  

The adult mouse subependymal zone provides a niche for mammalian neural stem cells (NSCs). However, the molecular signature, self-renewal potential, and fate behavior of NSCs remain poorly defined. Here we propose a model in which the fate of active NSCs is coupled to the total number of neighboring NSCs in a shared niche. Using knock-in reporter alleles and single-cell RNA sequencing, we show that the Wnt target Tnfrsf19/Troy identifies both active and quiescent NSCs. Quantitative analysis of genetic lineage tracing of individual NSCs under homeostasis or in response to injury reveals rapid expansion of stem-cell number before some return to quiescence. This behavior is best explained by stochastic fate decisions, where stem-cell number within a shared niche fluctuates over time. Fate mapping proliferating cells using a Ki67iresCreER allele confirms that active NSCs reversibly return to quiescence, achieving long-term self-renewal. Our findings suggest a niche-based mechanism for the regulation of NSC fate and number.


Cancers ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 3765
Author(s):  
Xiaoli Zhang ◽  
Kimerly Powell ◽  
Lang Li

Despite recent advances in diagnosis and treatment, breast cancer (BC) is still a major cause of cancer-related mortality in women. Breast cancer stem cells (BCSCs) are a small but significant subpopulation of heterogeneous breast cancer cells demonstrating strong self-renewal and proliferation properties. Accumulating evidence has proved that BCSCs are the driving force behind BC tumor initiation, progression, metastasis, drug resistance, and recurrence. As a heterogeneous disease, BC contains a full spectrum of different BC subtypes, and different subtypes of BC further exhibit distinct subtypes and proportions of BCSCs, which correspond to different treatment responses and disease-specific outcomes. This review summarized the current knowledge of BCSC biomarkers and their clinical relevance, the methods for the identification and isolation of BCSCs, and the mechanisms regulating BCSCs. We also discussed the cellular origin of BCSCs and the current advances in single-cell lineage tracing and transcriptomics and their potential in identifying the origin and lineage development of BCSCs.


EvoDevo ◽  
2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Nicholas D. Holland ◽  
Ildiko M. L. Somorjai

Abstract Background The cellular basis of adult growth in cephalochordates (lancelets or amphioxus) has received little attention. Lancelets and their constituent organs grow slowly but continuously during adult life. Here, we consider whether this slow organ growth involves tissue-specific stem cells. Specifically, we focus on the cell populations in the notochord of an adult lancelet and use serial blockface scanning electron microscopy (SBSEM) to reconstruct the three-dimensional fine structure of all the cells in a tissue volume considerably larger than normally imaged with this technique. Results In the notochordal region studied, we identified 10 cells with stem cell-like morphology at the posterior tip of the organ, 160 progenitor (Müller) cells arranged along its surface, and 385 highly differentiated lamellar cells constituting its core. Each cell type could clearly be distinguished on the basis of cytoplasmic density and overall cell shape. Moreover, because of the large sample size, transitions between cell types were obvious. Conclusions For the notochord of adult lancelets, a reasonable interpretation of our data indicates growth of the organ is based on stem cells that self-renew and also give rise to progenitor cells that, in turn, differentiate into lamellar cells. Our discussion compares the cellular basis of adult notochord growth among chordates in general. In the vertebrates, several studies implied that proliferating cells (chordoblasts) in the cortex of the organ might be stem cells. However, we think it is more likely that such cells actually constitute a progenitor population downstream from and maintained by inconspicuous stem cells. We venture to suggest that careful searches should find stem cells in the adult notochords of many vertebrates, although possibly not in the notochordal vestiges (nucleus pulposus regions) of mammals, where the presence of endogenous proliferating cells remains controversial.


2002 ◽  
Vol 283 (3) ◽  
pp. G767-G777 ◽  
Author(s):  
Matthew Bjerknes ◽  
Hazel Cheng

Previous studies of chimeric animals demonstrate that multipotential stem cells play a role in the development of the gastric epithelium; however, despite much effort, it is not clear whether they persist into adulthood. Here, chemical mutagenesis was used to label random epithelial cells by loss of transgene function in adult hemizygous ROSA26 mice, a mouse strain expressing the transgene lacZ in all tissues. Many clones derived from such cells contained all the major epithelial cell types, thereby demonstrating existence of functional multipotential stem cells in adult mouse gastric epithelium. We also observed clones containing only a single mature cell type, indicating the presence of long-lived committed progenitors in the gastric epithelium. Similar results were obtained in duodenum and colon, showing that this mouse model is suitable for lineage tracing in all regions of the gastrointestinal tract and likely useful for cell lineage studies in other adult renewing tissues.


Cell Reports ◽  
2020 ◽  
Vol 30 (5) ◽  
pp. 1463-1477.e7
Author(s):  
Ayesha Ali ◽  
Shafiq M. Syed ◽  
M. Fairuz B. Jamaluddin ◽  
Yolanda Colino-Sanguino ◽  
David Gallego-Ortega ◽  
...  

2014 ◽  
Vol 111 (50) ◽  
pp. 17983-17988 ◽  
Author(s):  
Hua Zhang ◽  
Lian Liu ◽  
Xin Li ◽  
Kiran Busayavalasa ◽  
Yan Shen ◽  
...  

2021 ◽  
pp. 002203452110137
Author(s):  
Y. Yi ◽  
W. Stenberg ◽  
W. Luo ◽  
J.Q. Feng ◽  
H. Zhao

Osseointegration is the key issue for implant success. The in vivo properties of cell populations driving the osseointegration process have remained largely unknown. In the current study, using tissue clearing–based 3-dimensional imaging and transgenic mouse model-based lineage tracing methods, we identified Gli1+ cells within alveolar bone marrow and their progeny as the cell population participating in extraction socket healing and implant osseointegration. These Gli1+ cells are surrounding blood vessels and do not express lineage differentiation markers. After tooth extraction and delayed placement of a dental implant, Gli1+ cells were activated into proliferation, and their descendants contributed significantly to new bone formation. Ablation of Gli1+ cells severely compromised the healing and osseointegration processes. Blockage of canonical Wnt signaling resulted in impaired recruitment of Gli1+ cells and compromised bone healing surrounding implants. Collectively, these findings demonstrate that Gli1+ cells surrounding alveolar bone marrow vasculature are stem cells supporting dental implant osseointegration. Canonical Wnt signal plays critical roles in regulating Gli1+ stem cells.


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