scholarly journals Maintenance of active chromatin states by Hmgn1 and Hmgn2 is required for stem cell identity:

2018 ◽  
Author(s):  
Sylvia Garza-Manero ◽  
Abdulmajeed A. A. Sindi ◽  
Gokula Mohan ◽  
Ohoud Rehbini ◽  
Valentine H. M. Jeantet ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Neuronal Differentiation ◽  
Embryonic Stem ◽  
Adult Brain ◽  
Active Chromatin ◽  
Cell Identity ◽  
Chromatin States ◽  
Neural Stem Progenitor Cells ◽  
Chromatin Configuration

Chromatin plasticity is thought to be fundamental to the pluripotency of embryonic stem cells. Hmgn proteins modulate chromatin structure and are highly expressed during early development and in neural stem/progenitor cells of the developing and adult brain. Here, we show that loss of Hmgn1 or Hmgn2 in pluripotent embryonal carcinoma cells leads to increased levels of spontaneous neuronal differentiation. This is accompanied by the loss of pluripotency markers and increased expression of the pro-neural transcription factors Neurog1 and Ascl1. Neural stem cells derived from these Hmgn-knockout lines also show increased spontaneous neuronal differentiation and Neurog1 expression. The loss of Hmgn2 is associated with the disruption of active chromatin states at specific classes of gene. The levels of H3K4me3, H3K9ac, H3K27ac and H3K122ac are considerably reduced at the pluripotency genes Nanog and Oct4, which impacts transcription. At endodermal/mesodermal lineage-specific genes, the loss of Hmgn2 leads to a switch from a bivalent to a repressive chromatin configuration. However, at the neuronal lineage genes Neurog1 and Ascl1, no epigenetic changes are observed and their bivalent states are retained. We conclude that Hmgn proteins play important roles in maintaining chromatin plasticity in stem cells, and are essential for maintaining stem cell identity and pluripotency.

scholarly journals Maintenance of active chromatin states by HMGN2 is required for stem cell identity in a pluripotent stem cell model

2019 ◽  
Vol 12 (1) ◽  
Author(s):  
Sylvia Garza-Manero ◽  
Abdulmajeed Abdulghani A. Sindi ◽  
Gokula Mohan ◽  
Ohoud Rehbini ◽  
Valentine H. M. Jeantet ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Neuronal Differentiation ◽  
Embryonal Carcinoma ◽  
Cell Model ◽  
Carcinoma Cells ◽  
Adult Brain ◽  
Embryonal Carcinoma Cells ◽  
Stem Cell Model ◽  
Neural Stem Progenitor Cells

Abstract Background Members of the HMGN protein family modulate chromatin structure and influence epigenetic modifications. HMGN1 and HMGN2 are highly expressed during early development and in the neural stem/progenitor cells of the developing and adult brain. Here, we investigate whether HMGN proteins contribute to the chromatin plasticity and epigenetic regulation that is essential for maintaining pluripotency in stem cells. Results We show that loss of Hmgn1 or Hmgn2 in pluripotent embryonal carcinoma cells leads to increased levels of spontaneous neuronal differentiation. This is accompanied by the loss of pluripotency markers Nanog and Ssea1, and increased expression of the pro-neural transcription factors Neurog1 and Ascl1. Neural stem cells derived from these Hmgn-knockout lines also show increased spontaneous neuronal differentiation and Neurog1 expression. The loss of HMGN2 leads to a global reduction in H3K9 acetylation, and disrupts the profile of H3K4me3, H3K9ac, H3K27ac and H3K122ac at the Nanog and Oct4 loci. At endodermal/mesodermal genes, Hmgn2-knockout cells show a switch from a bivalent to a repressive chromatin configuration. However, at neuronal lineage genes whose expression is increased, no epigenetic changes are observed and their bivalent states are retained following the loss of HMGN2. Conclusions We conclude that HMGN1 and HMGN2 maintain the identity of pluripotent embryonal carcinoma cells by optimising the pluripotency transcription factor network and protecting the cells from precocious differentiation. Our evidence suggests that HMGN2 regulates active and bivalent genes by promoting an epigenetic landscape of active histone modifications at promoters and enhancers.

scholarly journals Musashi1 Cooperates in Abnormal Cell Lineage Protein 28 (Lin28)-mediated Let-7 Family MicroRNA Biogenesis in Early Neural Differentiation

2011 ◽  
Vol 286 (18) ◽  
pp. 16121-16130 ◽  
Author(s):  
Hironori Kawahara ◽  
Yohei Okada ◽  
Takao Imai ◽  
Akio Iwanami ◽  
Paul S. Mischel ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Neural Differentiation ◽  
Rna Binding ◽  
Binding Protein ◽  
Embryonic Stem ◽  
Cell Lineage ◽  
Mirna Biogenesis ◽  
Neural Stem Progenitor Cells ◽  
Stem Cell Pluripotency

Musashi1 (Msi1) is an RNA-binding protein that is highly expressed in neural stem/progenitor cells (NS/PCs) as well as in other tissue stem cells. Msi1 binds to the 3′-UTR of its target mRNAs in NS/PCs, prevents their translation, and interferes with NS/PC differentiation. We previously showed that Msi1 competes with eIF4G to bind poly(A)-binding protein and inhibits assembly of the 80 S ribosome. Here we show that Msi1 works in concert with Lin28 to regulate post-transcriptional microRNA (miRNA) biogenesis in the cropping step, which occurs in the nucleus. Lin28 and its binding partner terminal uridylyltransferase 4 (TUT4) are known to maintain embryonic stem cell pluripotency by blocking let-7 miRNA biogenesis at the dicing step. Interestingly, we found that during early neural differentiation of embryonic stem cells, Msi1 enhanced the localization of Lin28 to the nucleus and also inhibited the nuclear cropping step of another let-7 family miRNA, miR98. These results suggest that Msi1 can influence stem cell maintenance and differentiation by controlling the subcellular localization of proteins involved in miRNA biogenesis, as well as by regulating the translation of its target mRNA.

Embryotoxicity of Lead (II) Acetate and Aroclor 1254 Using a New End Point of the Embryonic Stem Cell Test

2011 ◽  
Vol 30 (5) ◽  
pp. 498-509 ◽  
Author(s):  
Dae Hyun Baek ◽  
Sung Hee Park ◽  
Jae Hyun Park ◽  
Youngju Choi ◽  
Ki Dae Park ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Embryonic Stem Cells ◽  
Neuronal Differentiation ◽  
Embryonic Stem ◽  
Mouse Embryonic Stem Cells ◽  
Developmental Neurotoxicity ◽  
Aroclor 1254 ◽  
End Point ◽  
Cell Test

We developed a new end point of the mouse stem cell test (EST) for developmental neurotoxicity. We tested 2 developmental neurotoxicants, namely, lead (II) acetate and Aroclor 1254, using this EST. Our results showed that lead (II) acetate is nonembryotoxic, and Aroclor 1254 is weakly embryotoxic. To identify a new end point for developmental neurotoxicity, we used the default method of neuronal differentiation for D3 mouse embryonic stem cells with basic fibroblast growth factor (bFGF) and ascorbic acid. Flow cytometry and real-time polymerase chain reaction were used to quantify the inhibition of neuronal differentiation. Our results showed that both lead (II) acetate and Aroclor 1254 reduced the percentage of microtubule-associated protein 2 (MAP-2)-positive cells and the messenger RNA (mRNA) expression level of MAP-2 in a dose-dependent manner. These results suggested that these methods can be used to develop an additional end point of the EST for developmental neurotoxicity using default differentiation of mouse embryonic stem cells.

scholarly journals Role of miRNAs in Neuronal Differentiation from Human Embryonic Stem Cell—Derived Neural Stem Cells

2012 ◽  
Vol 8 (4) ◽  
pp. 1129-1137 ◽  
Author(s):  
Jing Liu ◽  
Jackline Githinji ◽  
Bridget Mclaughlin ◽  
Kasia Wilczek ◽  
Jan Nolta
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Neural Stem Cells ◽  
Embryonic Stem Cell ◽  
Neuronal Differentiation ◽  
Human Embryonic Stem Cell ◽  
Embryonic Stem

Progress in cerebral transplantation of expanded neuronal stem cells

2004 ◽  
Vol 100 (4) ◽  
pp. 659-671 ◽  
Author(s):  
R. Mark Richardson ◽  
Helen L. Fillmore ◽  
Kathryn L. Holloway ◽  
William C. Broaddus
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Large Body ◽  
Embryonic Stem ◽  
Adult Brain ◽  
Content Type ◽  
Neuronal Stem Cells ◽  
Primary Tissue ◽  
Fine Print

Object. Given the success and limitations of human fetal primary neural tissue transplantation, neuronal stem cells (NSCs) that can be adequately expanded in culture have been the focus of numerous attempts to develop a superior source of replacement cells for restorative neurosurgery. To clarify recent progress toward this goal, the transplantation into the adult brain of NSCs, expanded in vitro before grafting, was reviewed. Methods. Neuronal stem cells can be expanded from a variety of sources, including embryos, fetuses, adult bone marrow, and adult brain tissue. Recent investigations of each of these expanded stem cell types have generated a large body of information along with a great number of unanswered questions regarding the ability of these cells to replace damaged neurons. Expanded NSCs offer many advantages over their primary tissue predecessors, but also may exhibit different functional abilities as grafted cells. Because expanded NSCs will most likely ultimately replace primary tissue grafting in clinical trials, this review was undertaken to focus solely on this distinct body of work and to summarize clearly the existing preclinical data regarding the in vivo successes, limits, and unknowns of using each expanded NSC type when transplanted into the adult brain. Conclusions. Embryonic stem cell—derived cells have demonstrated appropriate neuronal phenotypes after transplantation into nonneurogenic areas of the adult brain. Understanding the mechanisms responsible for this may lead to similar success with less studied adult neuronal progenitor cells, which offer the potential for autologous NSC transplantation with less risk of tumorigenesis.

scholarly journals Inhibition of Notch Signaling in Human Embryonic Stem Cell-Derived Neural Stem Cells Delays G1/S Phase Transition and Accelerates Neuronal Differentiation In Vitro and In Vivo

Stem Cells ◽  
2010 ◽  
Vol 28 (5) ◽  
pp. 955-964 ◽  
Author(s):  
Lodovica Borghese ◽  
Dasa Dolezalova ◽  
Thoralf Opitz ◽  
Simone Haupt ◽  
Anke Leinhaas ◽  
...  
Keyword(s):  
Phase Transition ◽  
Stem Cells ◽  
Stem Cell ◽  
Notch Signaling ◽  
Neuronal Differentiation ◽  
Human Embryonic Stem Cell ◽  
Embryonic Stem ◽  
S Phase

Stem Cell-Based Therapies: A New Ray of Hope for Diabetic Patients

2019 ◽  
Vol 14 (2) ◽  
pp. 146-151 ◽  
Author(s):  
Junaid Khan ◽  
Amit Alexander ◽  
Mukta Agrawal ◽  
Ajazuddin ◽  
Sunil Kumar Dubey ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Drug Therapy ◽  
Type I Diabetes ◽  
Embryonic Stem ◽  
Health Concern ◽  
Future Research ◽  
Diabetic Patients ◽  
Successful Implementation ◽  
Type I

Diabetes and its complications are a significant health concern throughout the globe. There are physiological differences in the mechanism of type-I and type-II diabetes and the conventional drug therapy as well as insulin administration seem to be insufficient to address the problem at large successfully. Hypoglycemic swings, frequent dose adjustments and resistance to the drug are major problems associated with drug therapy. Cellular approaches through stem cell based therapeutic interventions offer a promising solution to the problem. The need for pancreatic transplants in case of Type- I diabetes can also be by-passed/reduced due to the formation of insulin producing β cells via stem cells. Embryonic Stem Cells (ESCs) and induced Pluripotent Stem Cells (iPSCs), successfully used for generating insulin producing β cells. Although many experiments have shown promising results with stem cells in vitro, their clinical testing still needs more exploration. The review attempts to bring into light the clinical studies favoring the transplantation of stem cells in diabetic patients with an objective of improving insulin secretion and improving degeneration of different tissues in response to diabetes. It also focuses on the problems associated with successful implementation of the technique and possible directions for future research.

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