Concise Review: Putting a Finger on Stem Cell Biology: Zinc Finger Nuclease-Driven Targeted Genetic Editing in Human Pluripotent Stem Cells

The clinical application of stem cells in hematopoietic disease. Use of pluripotent stem cells and their differentiated products in pharmacological drug discovery and safety testing. Messages from the nucleus: Insights into Aging. inStem: The Institute for Stem Cell Biology and Regenerative Medicine.

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Future perspective of induced pluripotent stem cells for diagnosis, drug screening and treatment of human diseases

Thrombosis and Haemostasis ◽

10.1160/th10-05-0269 ◽

2010 ◽

Vol 104 (07) ◽

pp. 39-44 ◽

Cited By ~ 27

Author(s):

Qizhou Lian ◽

Yenyen Chow ◽

Miguel Esteban ◽

Duanqing Pei ◽

Hung-Fat Tse

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Regenerative Medicine ◽

Induced Pluripotent Stem Cells ◽

Pluripotent Stem Cells ◽

Cell Biology ◽

Stem Cell Biology ◽

Ips Cell ◽

Cell Technology ◽

Induced Pluripotent

SummaryRecent advances in stem cell biology have transformed the understanding of cell physiology and developmental biology such that it can now play a more prominent role in the clinical application of stem cell and regenerative medicine. Success in the generation of human induced pluripotent stem cells (iPS) as well as related emerging technology on the iPS platform provide great promise in the development of regenerative medicine. Human iPS cells show almost identical properties to human embryonic stem cells (ESC) in pluripotency, but avoid many of their limitations of use. In addition, investigations into reprogramming of somatic cells to pluripotent stem cells facilitate a deeper understanding of human stem cell biology. The iPS cell technology has offered a unique platform for studying the pathogenesis of human disease, pharmacological and toxicological testing, and cell-based therapy. Nevertheless, significant challenges remain to be overcome before the promise of human iPS cell technology can be realised.

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Autophagy in Stem Cell Biology: A Perspective on Stem Cell Self-Renewal and Differentiation

Stem Cells International ◽

10.1155/2018/9131397 ◽

2018 ◽

Vol 2018 ◽

pp. 1-12 ◽

Cited By ~ 18

Author(s):

Xihang Chen ◽

Yunfan He ◽

Feng Lu

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Pluripotent Stem Cells ◽

Cell Biology ◽

Viral Infections ◽

Stem Cell Biology ◽

Self Renewal ◽

Cellular Homeostasis ◽

Intracellular Degradation ◽

Induced Pluripotent

Autophagy is a highly conserved cellular process that degrades modified, surplus, or harmful cytoplasmic components by sequestering them in autophagosomes which then fuses with the lysosome for degradation. As a major intracellular degradation and recycling pathway, autophagy is crucial for maintaining cellular homeostasis, as well as for remodeling during normal development. Impairment of this process has been implicated in various diseases, in the pathogenic response to bacterial and viral infections, and in aging. Pluripotent stem cells, with their ability to self-replicate and to give rise to any specialized cell type, are very valuable resources for cell-based medical therapies and open a number of promising avenues for studying human development and disease. It has been suggested that autophagy is vital for the maintenance of cellular homeostasis in stem cells, and subsequently more in-depth knowledge about the regulation of autophagy in stem cell biology has been acquired recently. In this review, we describe the most significant advances in the understanding of autophagy regulation in hematopoietic and mesenchymal stem cells, as well as in induced pluripotent stem cells. In particular, we highlight the roles of various autophagy activities in the regulation of self-renewal and differentiation of these stem cells.

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STAT3 for Cardiac Regenerative Medicine: Involvement in Stem Cell Biology, Pathophysiology, and Bioengineering

International Journal of Molecular Sciences ◽

10.3390/ijms21061937 ◽

2020 ◽

Vol 21 (6) ◽

pp. 1937 ◽

Cited By ~ 2

Author(s):

Shu Nakao ◽

Tasuku Tsukamoto ◽

Tomoe Ueyama ◽

Teruhisa Kawamura

Keyword(s):

Heart Failure ◽

Stem Cells ◽

Stem Cell ◽

Regenerative Medicine ◽

Pluripotent Stem Cells ◽

Cell Biology ◽

Cardiac Regeneration ◽

Janus Kinase ◽

Stem Cell Biology ◽

Stat3 Signaling

Heart disease is the most common cause of death in developed countries, but the medical treatments for heart failure remain limited. In this context, the development of cardiac regeneration therapy for severe heart failure is important. Owing to their unique characteristics, including multiple differentiation and infinitive self-renewal, pluripotent stem cells can be considered as a novel source for regenerative medicine. Janus kinase/signal transducer and activator of transcription 3 (JAK/STAT3) signaling plays critical roles in the induction, maintenance, and differentiation of pluripotent stem cells. In the heart, JAK/STAT3 signaling has diverse cellular functions, including myocardial differentiation, cell cycle re-entry of matured myocyte after injury, and anti-apoptosis in pathological conditions. Therefore, regulating STAT3 activity has great potential as a strategy of cardiac regeneration therapy. In this review, we summarize the current understanding of STAT3, focusing on stem cell biology and pathophysiology, as they contribute to cardiac regeneration therapy. We also introduce a recently reported therapeutic strategy for myocardial regeneration that uses engineered artificial receptors that trigger endogenous STAT3 signal activation.

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Fetal Stem Cells in Regenerative Medicine: Principles and Translational Strategies. Stem Cell Biology and Regenerative Medicine. Edited by Dario O. Fauza and Mahmud Bani. New York: Springer. $209.00. xix + 453 p.; ill.; index. ISBN: 978-1-4939-3481-2 (hc); 978-1-4939-3483-6 (eb). 2016.

The Quarterly Review of Biology ◽

10.1086/696795 ◽

2018 ◽

Vol 93 (1) ◽

pp. 59-59

Keyword(s):

Stem Cells ◽

New York ◽

Stem Cell ◽

Regenerative Medicine ◽

Cell Biology ◽

Stem Cell Biology ◽

Fetal Stem Cells ◽

Translational Strategies

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Zinc Finger Nuclease-Expressing Baculoviral Vectors Mediate Targeted Genome Integration of Reprogramming Factor Genes to Facilitate the Generation of Human Induced Pluripotent Stem Cells

Stem Cells Translational Medicine ◽

10.5966/sctm.2013-0043 ◽

2013 ◽

Vol 2 (12) ◽

pp. 935-945 ◽

Cited By ~ 16

Author(s):

Rui-Zhe Phang ◽

Felix Chang Tay ◽

Sal-Lee Goh ◽

Cia-Hin Lau ◽

Haibao Zhu ◽

...

Keyword(s):

Stem Cells ◽

Induced Pluripotent Stem Cells ◽

Zinc Finger ◽

Pluripotent Stem Cells ◽

Zinc Finger Nuclease ◽

Genome Integration ◽

Induced Pluripotent

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Concise Review: Asymmetric Cell Divisions in Stem Cell Biology

Symmetry ◽

10.3390/sym7042025 ◽

2015 ◽

Vol 7 (4) ◽

pp. 2025-2037 ◽

Cited By ~ 12

Author(s):

Florian Murke ◽

Symone Castro ◽

Bernd Giebel ◽

André Görgens

Keyword(s):

Stem Cell ◽

Cell Biology ◽

Stem Cell Biology ◽

Asymmetric Cell Divisions ◽

Cell Divisions ◽

Concise Review

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Pluripotent stem cell SOX9 and INS reporters facilitate differentiation into insulin-producing cells

10.1101/2021.02.02.429390 ◽

2021 ◽

Author(s):

Rabea Dettmer ◽

Isabell Niwolik ◽

Ilir Mehmeti ◽

Anne Jörns ◽

Ortwin Naujok

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Beta Cells ◽

Pluripotent Stem Cells ◽

Reporter Genes ◽

Human Pluripotent Stem Cells ◽

Endogenous Gene ◽

Pancreatic Progenitors ◽

Insulin Producing Cells ◽

Endogenous Genes

AbstractDifferentiation of human pluripotent stem cells into insulin-producing stem cell-derived beta cells harbors great potential for research and therapy of diabetes. The SOX9 gene plays a crucial role during development of the pancreas and particularly in the development of insulin-producing cells as SOX9+ cells form the source for NEUROG3+ endocrine progenitor cells. For the purpose of easy monitoring of differentiation efficiencies into pancreatic progenitors and insulin-producing cells, we generated new reporter lines by knocking in a P2A-H-2Kk-F2A-GFP2 reporter genes into the SOX9 locus and a P2A-mCherry reporter gene into the INS locus mediated by CRISPR/CAS9-technology. The knock-ins enable co-expression of the endogenous genes and reporter genes, report the endogenous gene expression and enable the purification of pancreatic progenitors and insulin-producing cells using FACS or MACS. Using these cell lines we established a new differentiation protocol geared towards SOX9+ cells to efficiently drive human pluripotent stem cells into glucose-responsive beta cells.

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Establishment of human OCT4 as a putative HSP90 client protein : a case for HSP90 chaperoning pluripotency

10.21504/10962/194010 ◽

2015 ◽

Author(s):

◽

Jason Neville Sterrenberg

Keyword(s):

Stem Cells ◽

Transcription Factor ◽

Stem Cell ◽

Cell Biology ◽

Therapeutic Potential ◽

Stem Cell Biology ◽

Client Protein ◽

Hsp90 Inhibition ◽

Regulated Gene Expression ◽

Hsp90 Client Protein

The therapeutic potential of stem cells is already being harnessed in clinical trails. Of even greater therapeutic potential has been the discovery of mechanisms to reprogram differentiated cells into a pluripotent stem cell-like state known as induced pluripotent stem cells (iPSCs). Stem cell nature is governed and maintained by a hierarchy of transcription factors, the apex of which is OCT4. Although much research has elucidated the transcriptional regulation of OCT4, OCT4 regulated gene expression profiles and OCT4 transcriptional activation mechanisms in both stem cell biology and cellular reprogramming to iPSCs, the fundamental biochemistry surrounding the OCT4 transcription factor remains largely unknown. In order to analyze the biochemical relationship between HSP90 and human OCT4 we developed an exogenous active human OCT4 expression model with human OCT4 under transcriptional control of a constitutive promoter. We identified the direct interaction between HSP90 and human OCT4 despite the fact that the proteins predominantly display differential subcellular localizations. We show that HSP90 inhibition resulted in degradation of human OCT4 via the ubiquitin proteasome degradation pathway. As human OCT4 and HSP90 did not interact in the nucleus, we suggest that HSP90 functions in the cytoplasmic stabilization of human OCT4. Our analysis suggests HSP90 inhibition inhibits the transcriptional activity of human OCT4 dimers without affecting monomeric OCT4 activity. Additionally our data suggests that the HSP90 and human OCT4 complex is modulated by phosphorylation events either promoting or abrogating the interaction between HSP90 and human OCT4. Our data suggest that human OCT4 displays the characteristics describing HSP90 client proteins, therefore we identify human OCT4 as a putative HSP90 client protein. The regulation of the transcription factor OCT4 by HSP90 provides fundamental insights into the complex biochemistry of stem cell biology. This may also be suggestive that HSP90 not only regulates stem cell biology by maintaining routine cellular homeostasis but additionally through the direct regulation of pluripotency factors.

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3. Personalized pluripotent stem cells

10.1093/actrade/9780198869290.003.0003 ◽

2021 ◽

pp. 39-51

Author(s):

Jonathan Slack

Keyword(s):

Stem Cells ◽

Pluripotent Stem Cells ◽

Cell Biology ◽

Nuclear Transplantation ◽

Stem Cell Biology ◽

Normal Cells ◽

Specific Patient ◽

No Formation ◽

Induced Pluripotent ◽

The Individual

‘Personalized pluripotent stem cells’ discusses cloning and its connection to stem cell biology. Somatic cell nuclear transplantation into oocytes can make personalized pluripotent stem cells as a perfect genetic match to a specific patient that provoke no immune rejection on grafting. Because this procedure involves generation of cells but no formation of an actual cloned individual, it has become known as human therapeutic cloning. Induced pluripotent stem cells (iPS cells) are made by introducing a few specific genes into normal cells. They are also a perfect genetic match to the individual donating the normal cells and because they are easy to make are now the preferred source.

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