Stem Cells
- Pluripotent stem cell energy metabolism: an update
- 1Molecular Biology Institute, University of California, Los Angeles, CA, USA
- 2Department of Pathology and Laboratory Medicine, University of California, Los Angeles, CA, USA
- 3Department of Bioengineering, University of California, Los Angeles, CA, USA
- 4Department of Pediatrics, University of California, Los Angeles, CA, USA
- 5California NanoSystems Institute, University of California, Los Angeles, CA, USA
- 6Jonsson Comprehensive Cancer Center, University of California, Los Angeles, CA, USA
- 7Broad Center of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, CA, USA
- ↵*Corresponding author. Tel: +1 310 206 6754; Fax: +1 310 267 0382; E‐mail: mteitell{at}mednet.ucla.edu
The metabolic capacity, mitochondrial activity, and the potential of cells to self‐renew/to be reprogrammed are intimately connected. This timely review features most recent advances in pluripotent stem cell energetics.
The EMBO Journal (2015) 34: 138–153
- Received October 31, 2014.
- Revision received November 15, 2014.
- Accepted November 17, 2014.
- © 2014 The Authors
- Regulation of Drosophila intestinal stem cell maintenance and differentiation by the transcription factor Escargot
- Mariano A Loza‐Coll1,2,
- Tony D Southall3,5,
- Sharsti L Sandall1,
- Andrea H Brand3 and
- D Leanne Jones*,1,2,4
- 1Laboratory of Genetics, The Salk Institute for Biological Studies, La Jolla, CA, USA
- 2Department of Molecular, Cell, and Developmental Biology, University of California Los Angeles, Los Angeles, CA, USA
- 3The Gurdon Institute University of Cambridge, Cambridge, UK
- 4Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California Los Angeles, Los Angeles, CA, USA
- 5Department of Life Sciences, Imperial College London, London, UK
- ↵*Corresponding author. Tel: +1 310 206 7066; E‐mail: leannejones{at}ucla.edu
These authors uncover a dual role of Escargot (Esg) in Drosophila intestinal stem cell homeostasis: While regulating stem cell maintenance, Esg also controls Notch‐dependent enteroblast differentiation via its direct target gene Amun.
Synopsis
These authors uncover a dual role of Escargot (Esg) in Drosophila intestinal stem cell homeostasis: While regulating stem cell maintenance, Esg also controls Notch‐dependent enteroblast differentiation via its direct target gene Amun.
Escargot (Esg) is required for intestinal stem cell (ISC) maintenance.
Loss of Esg biases the fate of ISCs towards the enteroendocrine (EE) lineage.
Esg positively modulates Notch in enteroblasts (EBs) through repression of Amun.
The EMBO Journal (2014) 33: 2983–2996
- Received May 21, 2014.
- Revision received October 20, 2014.
- Accepted October 27, 2014.
- © 2014 The Authors
- How stem cells get “turned on”
- Amy J Wagers (amy_wagers{at}harvard.edu)1
Recent research began to link autophagic processes to the functional integrity of certain stem cells. A novel study published in this issue of The EMBO Journal reports on autophagic flux as crucial checkpoint to meet the energy demands during muscle stem cell activation.
See also: AH Tang & TA Rando (December 2014)
Activation of muscle stem cells requires defined energy levels. Recent results determine autophagic flux as crucial contributor to the metabolic state of muscle stem cells.
- © 2014 The Author
- Induction of autophagy supports the bioenergetic demands of quiescent muscle stem cell activation
- 1Paul F. Glenn Center for the Biology of Aging, Stanford University School of Medicine, Stanford, CA, USA
- 2Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA, USA
- 3Neurology Service and Rehabilitation Research and Developmental Center of Excellence, Veterans Affairs Palo Alto Health Care System, Palo Alto, CA, USA
- ↵*Corresponding author. Tel: +1 650 849 1999; E‐mail: rando{at}stanford.edu
↵† This article has been contributed to by US Government employees and their work is in the public domain in the USA
Tang and Rando report induction of autophagy by the nutrient sensor SIRT1 as crucial energy provider for efficient proliferation/differentiation in quiescent muscle satellite cells in vivo.
Synopsis
Tang and Rando report induction of autophagy by the nutrient sensor SIRT1 as crucial energy provider for efficient proliferation/differentiation in quiescent muscle satellite cells in vivo.
Muscle stem cells require autophagy to surmount a bioenergetic hurdle to break quiescence to enter an activated state.
Bioenergetic demands accompanying muscle stem cell activation induces autophagic flux.
These bioenergetic demands are signaled through SIRT1 to activate autophagy by interaction with ATG7 and through the AMPK pathway.
The EMBO Journal (2014) 33: 2782–2797
- Received February 19, 2014.
- Revision received August 29, 2014.
- Accepted September 1, 2014.
- © 2014 The Authors
- Escargot maintains stemness and suppresses differentiation in Drosophila intestinal stem cells
- Jerome Korzelius1,
- Svenja K Naumann1,
- Mariano A Loza‐Coll2,3,
- Jessica SK Chan1,
- Devanjali Dutta1,
- Jessica Oberheim1,
- Christine Gläßer1,
- Tony D Southall4,5,
- Andrea H Brand4,
- D Leanne Jones2,3 and
- Bruce A Edgar*,1
- 1DKFZ/ZMBH Alliance, University of Heidelberg, Heidelberg, Germany
- 2Laboratory of Genetics, The Salk Institute for Biological Studies, La Jolla, CA, USA
- 3Department of Molecular, Cell, and Developmental Biology, University of California‐Los Angeles, Los Angeles, CA, USA
- 4The Gurdon Institute and Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, UK
- 5Department of Life Sciences, Imperial College London, London, UK
- ↵*Corresponding author. Tel: +49 6221 54 6827; Fax: +49 6221 54 5891; E‐mail: b.edgar{at}Dkfz-Heidelberg.de
This paper unravels the functionality of Escargot, so far described as marker for progenitors cells in Drosophila, in intestinal stem cell maintenance and suppressor of differentiation.
Synopsis
This paper unravels the functionality of Escargot, so far described as marker for progenitors cells in Drosophila, in intestinal stem cell maintenance and suppressor of differentiation.
Esg is required to maintain intestinal stem cell identity.
Esg acts as a repressor of differentiation genes in progenitor cells.
Pdm1 is a direct target of Esg that is sufficient to trigger EC differentiation.
Esg, Notch and Pdm1 function together in a transcriptional network that controls differentiation in the Drosophila midgut.
The EMBO Journal (2014) 33: 2967–2982
- Received May 22, 2014.
- Revision received August 25, 2014.
- Accepted September 12, 2014.
- © 2014 The Authors. Published under the terms of the CC BY NC ND 4.0 license
This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs 4.0 License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
- Discrete Notch signaling requirements in the specification of hematopoietic stem cells
- Albert D Kim1,
- Chase H Melick1,
- Wilson K Clements1,2,
- David L Stachura1,
- Martin Distel1,
- Daniela Panáková3,4,
- Calum MacRae4,
- Lindsey A Mork5,
- J Gage Crump5 and
- David Traver*,1,6
- 1Department of Cellular and Molecular Medicine, University of California at San Diego, La Jolla, CA, USA
- 2Department of Hematology, St. Jude Children's Research Hospital, Memphis, TN, USA
- 3Max Delbrück Center for Molecular Medicine, Berlin‐Buch, Germany
- 4Cardiovascular Division, Brigham and Women's Hospital Harvard Medical School, Boston, MA, USA
- 5Department of Stem Cell Biology and Regenerative Medicine, University of Southern California Keck School of Medicine, Los Angeles, CA, USA
- 6Section of Cell and Developmental Biology, University of California at San Diego, La Jolla, CA, USA
- ↵*Corresponding author. Tel: +1 858 822 4593; E‐mail: dtraver{at}ucsd.edu
This paper dissects the contributions of discrete Notch‐signaling events during HSC generation.
Synopsis
This paper dissects the contributions of discrete Notch‐signaling events during HSC generation.
We demonstrate independent functional requirements for three Notch receptors in the specification of HSCs in zebrafish.
Notch1a/1b function cell‐autonomously in the precursors of hemogenic endothelium during dorsal aorta formation.
Conversely, Notch3 determines sclerotome fate in a non‐cell‐autonomous manner.
Notch3 operates downstream of Wnt16 during HSC specification.
The EMBO Journal (2014) 33: 2363–2373
- Received April 21, 2014.
- Revision received July 26, 2014.
- Accepted August 11, 2014.
- © 2014 The Authors
- Deep diving in the blood stem cell‐ome
Defining the functional distinctions between cells comprising the bone marrow has yielded fundamental insights into lineage ordering and drivers of blood cell production. A novel, highly granular and multi‐dimensional molecular characterization of functional subsets of hematopoietic stem‐ and progenitor cells recently published in Cell Stem Cell (Cabezas‐Wallscheid et al, 2014) will serve as a landmark and treasure trove for unanticipated insights into basic biology and the development of future targeted medicine.
See also: N Cabezas‐Wallscheid et al
An integrated ‐omics analysis of hematopoietic stem‐ and progenitor populations offers unprecedented insights into their regulatory networks at the molecular, cellular and epigenetic level.
- © 2014 The Authors
- Stem cell competition: how speeding mutants beat the rest
How mutations lead to tumor formation is a central question in cancer research. Although cellular changes that follow the occurrence of common mutations are well characterized, much less is known about their effects on the population level. Now, two recent studies reveal in what way oncogenic aberrations alter stem cell dynamics to provide cells with an evolutionary advantage over their neighbors (Amoyel et al, 2014; Baker et al, 2014).
See also: M Amoyel et al (October 2014) and
AM Baker et al (August 2014)
A new study on clonal tracing in human tissue validates the concept of neutral competition, earlier revealed by genetic manipulation in various model organisms.
- © 2014 The Authors
- Taming the young and restless—epigenetic gene regulation in pancreas and beta‐cell precursors
The in vivo assessment of epigenetic changes during mouse pancreatic beta‐cell differentiation reveals surprising differences to directed, in vitro differentiation of human embryonic stem cells. New findings reported in this issue of The EMBO Journal further identify Ezh2 as a critical determinant of endocrine progenitor number and could instruct improved protocols for stem cell‐based therapies.
See also: CR Xu et al (October 2014)
A new study reports genome‐wide occupancy maps of H3K27me3 during pancreatic progenitor differentiation. The functional perturbation of Ezh2 increases endocrine progenitor fate and could thus inform therapeutically relevant differentiation protocols.
- © 2014 The Authors
- Dynamics of genomic H3K27me3 domains and role of EZH2 during pancreatic endocrine specification
- Cheng‐Ran Xu1,2,
- Lin‐Chen Li2,
- Greg Donahue1,
- Lei Ying3,
- Yu‐Wei Zhang2,
- Paul Gadue3 and
- Kenneth S Zaret*,1
- 1Institute for Regenerative Medicine, Epigenetics Program, Department of Cell and Developmental Biology, Perelman School of Medicine University of Pennsylvania, Philadelphia, PA, USA
- 2Ministry of Education Key Laboratory of Cell Proliferation, College of Life Sciences Peking‐Tsinghua Center for Life Sciences Peking University, Beijing, China
- 3Department of Pathology and Laboratory Medicine, Center for Cellular and Molecular Therapeutics, Children's Hospital of Philadelphia, Philadelphia, PA, USA
- ↵*Corresponding author. Tel: +1 215 573 5813; E‐mail: zaret{at}upenn.edu
The in vivo analysis of Ezh2‐dependent H3K27me3‐dynamics during pancreatic endocrine specification could instruct optimized ES cell differentiation for future therapeutic application.
Synopsis
The in vivo analysis of Ezh2‐dependent H3K27me3‐dynamics during pancreatic endocrine specification could instruct optimized ES cell differentiation for future therapeutic application.
During pancreatic endocrine development in embryos, genes that gain H3K27me3 typically are involved in cell biology and morphogenesis, whereas genes that lose H3K27me3 are typically involved in developmental gene regulation.
The gain in H3K27me3 domains observed in pancreas development in embryos differs from the decline in such domains reported for ES cell differentiation to pancreas progenitors in vitro.
Genetic diminution of Ezh2 at the pancreas progenitor stage in embryos enhances the subsequent production of endocrine progenitors and beta cells.
Inhibition of EZH2 at the endocrine progenitor induction stage in differentiating human ES cells increases the production of beta‐like cells in vitro.
The EMBO Journal (2014) 33: 2157–2170
- Received April 6, 2014.
- Revision received July 11, 2014.
- Accepted July 16, 2014.
- © 2014 The Authors
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