Why isn’t sex optional? Stem-cell competition, loss of regenerative capacity, and cancer in metazoan evolution

AbstractAxon regeneration is orchestrated by many genes that are differentially expressed in response to injury. Through a comparative analysis of gene expression profiling, injury-responsive genes that are potential targets for understanding the mechanisms underlying regeneration have been revealed. As the efficiency of axon regeneration in both the peripheral and central nervous systems can be manipulated, we suggest that identifying regeneration-associated genes is a promising approach for developing therapeutic applications in vivo. Here, we review the possible roles of stem cell marker- or stemness-related genes in axon regeneration to gain a better understanding of the regeneration mechanism and to identify targets that can enhance regenerative capacity.

Download Full-text

Accelerated erythroid repopulation with no stem-cell competition effect in children treated with recombinant human erythropoietin after allogeneic bone marrow transplantation

British Journal of Haematology ◽

10.1111/j.1365-2141.1993.tb03158.x ◽

1993 ◽

Vol 84 (4) ◽

pp. 752-754 ◽

Cited By ~ 14

Author(s):

Franco Locatelli ◽

Marco Zecca ◽

Yves Beguin ◽

Giovanna Giorgiani ◽

Luisa Ponchio ◽

...

Keyword(s):

Bone Marrow ◽

Stem Cell ◽

Bone Marrow Transplantation ◽

Marrow Transplantation ◽

Recombinant Human Erythropoietin ◽

Allogeneic Bone Marrow Transplantation ◽

Allogeneic Bone ◽

Competition Effect ◽

Cell Competition ◽

Human Erythropoietin

Download Full-text

Designing stem cell niches for differentiation and self-renewal

Journal of The Royal Society Interface ◽

10.1098/rsif.2018.0388 ◽

2018 ◽

Vol 15 (145) ◽

pp. 20180388 ◽

Cited By ~ 35

Author(s):

Hannah Donnelly ◽

Manuel Salmeron-Sanchez ◽

Matthew J. Dalby

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Regenerative Medicine ◽

Regulatory Networks ◽

Regulatory Mechanisms ◽

Great Promise ◽

Regenerative Capacity ◽

Cell Niche ◽

Stem Cell Niches

Mesenchymal stem cells, characterized by their ability to differentiate into skeletal tissues and self-renew, hold great promise for both regenerative medicine and novel therapeutic discovery. However, their regenerative capacity is retained only when in contact with their specialized microenvironment, termed the stem cell niche . Niches provide structural and functional cues that are both biochemical and biophysical, stem cells integrate this complex array of signals with intrinsic regulatory networks to meet physiological demands. Although, some of these regulatory mechanisms remain poorly understood or difficult to harness with traditional culture systems. Biomaterial strategies are being developed that aim to recapitulate stem cell niches, by engineering microenvironments with physiological-like niche properties that aim to elucidate stem cell-regulatory mechanisms, and to harness their regenerative capacity in vitro . In the future, engineered niches will prove important tools for both regenerative medicine and therapeutic discoveries.

Download Full-text

Confetti illuminates the cryptic way calorie restriction protects from cancer

Science Translational Medicine ◽

10.1126/scitranslmed.abd4765 ◽

2020 ◽

Vol 12 (555) ◽

pp. eabd4765

Author(s):

Emily J. Gallagher

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Calorie Restriction ◽

Intestinal Stem Cell ◽

Cell Competition

Calorie restriction increases intestinal stem cell competition and decreases the retention of stem cells with mutations in mice.

Download Full-text

A transit-amplifying population underpins the efficient regenerative capacity of the testis

Journal of Experimental Medicine ◽

10.1084/jem.20161371 ◽

2017 ◽

Vol 214 (6) ◽

pp. 1631-1641 ◽

Cited By ~ 26

Author(s):

Claudia Carrieri ◽

Stefano Comazzetto ◽

Amit Grover ◽

Marcos Morgan ◽

Andreas Buness ◽

...

Keyword(s):

Stem Cell ◽

Tissue Repair ◽

Cell Activity ◽

Adult Life ◽

Spermatogonial Stem Cell ◽

Mouse Testis ◽

Regenerative Capacity ◽

Cell Pool ◽

Stem Cell Activity ◽

Stem Cell Pool

The spermatogonial stem cell (SSC) that supports spermatogenesis throughout adult life resides within the GFRα1-expressing A type undifferentiated spermatogonia. The decision to commit to spermatogenic differentiation coincides with the loss of GFRα1 and reciprocal gain of Ngn3 (Neurog3) expression. Through the analysis of the piRNA factor Miwi2 (Piwil4), we identify a novel population of Ngn3-expressing spermatogonia that are essential for efficient testicular regeneration after injury. Depletion of Miwi2-expressing cells results in a transient impact on testicular homeostasis, with this population behaving strictly as transit amplifying cells under homeostatic conditions. However, upon injury, Miwi2-expressing cells are essential for the efficient regenerative capacity of the testis, and also display facultative stem activity in transplantation assays. In summary, the mouse testis has adopted a regenerative strategy to expand stem cell activity by incorporating a transit-amplifying population to the effective stem cell pool, thus ensuring rapid and efficient tissue repair.

Download Full-text