Hematopoietic Stem Cell Responsiveness to Exogenous Signals Is Limited by Caspase-3

Janzen, Viktor; Fleming, Heather E.; Riedt, Tamara; Karlsson, Göran; Riese, Matthew J.; Celso, Cristina Lo; Reynolds, Griffin; Milne, Craig D.; Paige, Christopher J.; Karlsson, Stefán; Woo, Minna; Scadden, David T.

doi:10.1016/j.stem.2008.03.012

Cited by 108 publications

(131 citation statements)

References 34 publications

(42 reference statements)

Supporting

Mentioning

122

Contrasting

Unclassified

Order By: Relevance

“…90 Caspase-7 has an additional role in proper functioning of odontoblasts as caspase-7 knockout mice show reduced dental mineralization. 91 A role for caspase-3 in differentiation of embryonic stem cells (ESCs) and hematopoietic stem cells (HSCs) has also been reported, 92,93 with caspase-3 deficiency-impeding differentiation Haematopoietic stem cell Caspase-3 Maintenance of stem-cell quiescence and response to external stimuli 93 New functions for old molecules S Shalini et al of these stem cell populations. Caspase activity is also required for macrophage colony-stimulating factor (M-CSF)-mediated differentiation of human peripheral blood monocytes.…”

Section: Caspases In Cell-fate Determination and Differentiationmentioning

confidence: 99%

Old, new and emerging functions of caspases

et al. 2014

View full text Add to dashboard Cite

Caspases are proteases with a well-defined role in apoptosis. However, increasing evidence indicates multiple functions of caspases outside apoptosis. Caspase-1 and caspase-11 have roles in inflammation and mediating inflammatory cell death by pyroptosis. Similarly, caspase-8 has dual role in cell death, mediating both receptor-mediated apoptosis and in its absence, necroptosis. Caspase-8 also functions in maintenance and homeostasis of the adult T-cell population. Caspase-3 has important roles in tissue differentiation, regeneration and neural development in ways that are distinct and do not involve any apoptotic activity. Several other caspases have demonstrated anti-tumor roles. Notable among them are caspase-2, -8 and -14. However, increased caspase-2 and -8 expression in certain types of tumor has also been linked to promoting tumorigenesis. Increased levels of caspase-3 in tumor cells causes apoptosis and secretion of paracrine factors that promotes compensatory proliferation in surrounding normal tissues, tumor cell repopulation and presents a barrier for effective therapeutic strategies. Besides this caspase-2 has emerged as a unique caspase with potential roles in maintaining genomic stability, metabolism, autophagy and aging. The present review focuses on some of these less studied and emerging functions of mammalian caspases.

show abstract

Section: Caspases In Cell-fate Determination and Differentiationmentioning

confidence: 99%

Old, new and emerging functions of caspases

et al. 2014

View full text Add to dashboard Cite

show abstract

“…However, restoration of active MST1 in caspase null myoblasts provides only a partial rescue of the differentiation defect, indicating that caspase activity must engage additional substrates to promote or sustain nondeath cell-fate outcomes (6). Other reports have shown that caspase 3 regulates differentiation indirectly by targeting and inactivating proteins that maintain stem-cell self-renewal/pluripotency (8,9). Although these later interactions contribute to the caspase effect, the targeting of these proteins does not explain the widespread alterations in gene expression and genomic reprogramming that typify differentiation.…”

mentioning

confidence: 99%

Caspase 3/caspase-activated DNase promote cell differentiation by inducing DNA strand breaks

Larsen

Rampalli

Burns

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

217

204

View full text Add to dashboard Cite

Caspase 3 is required for the differentiation of a wide variety of cell types, yet it remains unclear how this apoptotic protein could promote such a cell-fate decision. Caspase signals often result in the activation of the specific nuclease caspase-activated DNase (CAD), suggesting that cell differentiation may be dependent on a CADmediated modification in chromatin structure. In this study, we have investigated if caspase 3/CAD plays a role in initiating the DNA strand breaks that are known to occur during the terminal differentiation of skeletal muscle cells. Here, we show that inhibition of caspase 3 or reduction of CAD expression leads to a dramatic loss of strand-break formation and a block in the myogenic program. Caspase-dependent induction of differentiation results in CAD targeting of the p21 promoter, and loss of caspase 3 or CAD leads to a significant down-regulation in p21 expression. These results show that caspase 3/CAD promotes cell differentiation by directly modifying the DNA/nuclear microenvironment, which enhances the expression of critical regulatory genes.development | gene expression | non-apoptotic caspase activity | epigenetics

show abstract

“…Sox2, on the other hand, is expressed by fetal and adult neural stem cells and is required for their selfrenewal (Graham et al 2003;Suh et al 2007). Caspase-3 deficiency increases adult HSC numbers (Janzen et al 2008) just as it promotes the maintenance of ES cells (Fujita et al 2008). The Zfx transcription factor provides a particularly interesting example because it is required for the self-renewal of adult (but not fetal) HSCs in addition to ES cells (Galan-Caridad et al 2007).…”

Section: Fetal Germ-line Stem Cellsmentioning

confidence: 99%

Stem Cells Use Distinct Self-renewal Programs at Different Ages

Levi¹,

Morrison²

2008

Cold Spring Harbor Symposia on Quantitative Biology

View full text Add to dashboard Cite

Stem cells expand in number during development and persist throughout life by undergoing self-renewing divisions. The question of how stem cells self-renew throughout life is a fundamental problem in cell biology, with broad implications for understanding development, tissue regeneration, cancer, and aging. Recent insights demonstrate that self-renewal programs depend on key transcriptional regulators that are often shared among stem cells in different tissues but that often change between stem cells at different stages of life: Embryonic, fetal, young adult, and old adult stem cells are maintained by different self-renewal programs. Self-renewal programs change over time to contend with changes in tissue growth and repair demands as well as the increasing risk of malignant transformation during aging. The downstream mechanisms by which these programs regulate the cell cycle, developmental potential, and timing of differentiation are just starting to be elucidated. One key requirement for self-renewal is repression of the p16 Ink4a and p19 Arf tumor suppressors. This is accomplished by overlapping transcriptional regulators whose expression and function change with age, so as to maintain self-renewal potential throughout life while allowing increased expression of p16 Ink4a and p19 Arf in aging stem cells. This reduces stem cell function in aging tissues but also reduces cancer incidence.

show abstract

Hematopoietic Stem Cell Responsiveness to Exogenous Signals Is Limited by Caspase-3

Cited by 108 publications

References 34 publications

Old, new and emerging functions of caspases

Old, new and emerging functions of caspases

Caspase 3/caspase-activated DNase promote cell differentiation by inducing DNA strand breaks

Stem Cells Use Distinct Self-renewal Programs at Different Ages

Contact Info

Product

Resources

About