Histone H2A deubiquitinase BAP1 is essential for endothelial cell differentiation from human pluripotent stem cells.

Polycomb group proteins (PcGs) add repressive post translational histone modifications such as H2AK119ub1, and histone H2A deubiquitinases remove it. Mice lacking histone H2A deubiquitinases such as Usp16 and Bap1 die in embryonic stage, while mice lacking Usp3, Mysm1, Usp12, and Usp21 have been shown to be deficient in hematopoietic lineage differentiation, cell cycle regulation, and DNA repair. Thus, it is likely that histone deubiquitinases may also be required for human endothelial cell differentiation; however, there are no reports about the role of histone H2A deubiquitinase BAP1 in human endothelial cell development.

Assessment of human embryonic stem cells differentiation into definitive endoderm lineage on the soft substrates.

Pluripotent stem cells (PSCs) hold enormous potential for treating multiple diseases owing to their ability to self-renew and differentiate into any cell type. Albeit possessing such promising potential, controlling their differentiation into a desired cell type continues to be a challenge. Recent studies suggest that PSCs respond to different substrate stiffness and, therefore, can differentiate towards some lineages via Hippo pathway.

The Molecular Mechanisms Involved in the Hypertrophic Scars Post-Burn Injury.

Scar formation is a normal response to skin injuries. During the scar-remodeling phase, scar tissue is usually replaced with normal, functional tissue. However, after deep burn injuries, the scar tissue may persist and lead to contractures around joints, a condition known as hypertrophic scar tissue.

The symbiotic effect of osteoinductive extracellular vesicles and mineralized microenvironment on osteogenesis.

The increasing prevalence of bone-related diseases has raised concern about the need for an osteoinductive and mechanically stronger scaffold-based bone tissue engineering (BTE) alternative. A mineralized microenvironment, similar to the native bone microenvironment, is required in the scaffold to recruit and differentiate local mesenchymal stem cells at the bone defect site. Further, extracellular vesicles (EVs), pre-osteoblasts' secretome, contain osteoinductive cargo and have recently been exploited in bone regeneration.

Retinoic acid signaling is critical for generation of pancreatic progenitors from human embryonic stem cells.

Retinoic acid (RA) is essential for gut endoderm development and has been extensively used for pancreatic differentiation from human pluripotent stem cells. However, the gene regulatory network triggered by RA signaling remains poorly addressed. Also, whether RA signals control histone modifiers such as the Polycomb group proteins during pancreatic specification remains to be explored.

Soft substrate maintains stemness and pluripotent stem cell-like phenotype of human embryonic stem cells under defined culture conditions.

Unlabelled: Human embryonic stem cells (hESCs) are derived from the inner cell mass (ICM) of the pre-implantation blastocyst. Prior to embryo implantation the ICM cells are surrounded by trophoblasts which have mechanical stiffness ranging from Pascal (Pa) to kilopascal (kPa). However, under in vitro conditions these cells are cultured on stiff tissue culture treated plastic plates (TCP) which have stiffness of approximately 1 gigapascal (GPa).

Differential expression of retinoic acid alpha and beta receptors in neuronal progenitors generated from human embryonic stem cells in response to TTNPB (a retinoic acid mimetic).

Retinoic acid (RA), an active metabolite of vitamin A, plays a critical role in the morphogenesis and differentiation of various tissues, especially in the central nervous system. RA is the most commonly used morphogen for the differentiation of human embryonic stem cells (hESCs) into neuronal progenitor cells (NPCs), an abundant source of healthy neuronal tissues for regenerative therapy. During the differentiation process, the activity of RA is governed by the involvement of RA receptor subtypes (RAR α, β, and γ) and their isoforms in the nucleus.

Deterministic role of sonic hedgehog signalling pathway in specification of hemogenic versus endocardiogenic endothelium from differentiated human embryonic stem cells.

Embryonic stem cells (ESCs) have been shown to have an ability to form a large number of functional endothelial cells in vitro, but generating organ-specific endothelial cells remains a challenge. Sonic hedgehog (SHH) pathway is one of the crucial developmental pathways that control differentiation of many embryonic cell types such as neuroectodermal, primitive gut tube and developing limb buds; SHH pathway is important for functioning of adult cell of skin, bone, liver as well as it regulates haematopoiesis. Misregulation of SHH pathway leads to cancers such as hepatic, pancreatic, basal cell carcinoma, medulloblastoma, etc.

ChIP-qPCR for Polycomb Group Proteins During Neuronal Differentiation of Human Pluripotent Stem Cells.

Neuronal differentiation is an intricate and a complex process which involves crosstalk among various signaling pathways, growth factors, transcription factors, and epigenetic modifiers. During different stages of neuronal development, there are various histone modifiers which drive the expression of lineage-specific genes. Polycomb group proteins are one of the histone modifiers that control transcriptional repression of specific genes in development, differentiation, and functionality of various tissues.

Placenta: A gold mine for translational research and regenerative medicine.

Stem cell therapy has gained much impetus in regenerative medicine due to some of the encouraging results obtained in the laboratory as well as in translational/clinical studies. Although stem cells are of various types and their therapeutic potential has been documented in several studies, mesenchymal stromal/stem cells (MSCs) have an edge, as in addition to being multipotent, these cells are easy to obtain and expand, pose fewer ethical issues, and possess immense regenerative potential when used in a scientifically correct manner. Currently, MSCs are being sourced from various tissues such as bone marrow, cord, cord blood, adipose tissue, dental tissue, etc.

Sonic hedgehog signals hinder the transcriptional network necessary for pancreatic endoderm formation from human embryonic stem cells.

Hedgehog morphogens govern multiple aspects of pancreas organogenesis and functioning with diverse outcomes across species. Although most current differentiation protocols repress Sonic hedgehog (SHH) signals during in vitro endocrine specification, the role and mechanisms through which the SHH pathway antagonizes pancreas development during in vitro human embryonic stem (hES) cell differentiation remain unclear. We modulated SHH signaling at transitory stages of hES cell-derived pancreatic progenitors and analyzed the effect on cellular fate decisions.

Effect of Sonic hedgehog pathway inhibition on PDX1 expression during pancreatic differentiation of human embryonic stem cells.

Differentiation processes for generating pancreatic progenitors from pluripotent stem cells inhibit Sonic hedgehog signaling through synthetic antagonists. However, the effect of sonic hedgehog inhibition in differentiating human embryonic stem cells remains unclear. The primary aim of this study was to understand the effect of Sonic hedgehog inhibition on key pancreas-specific transcription factors during differentiation of human embryonic stem cells towards a pancreatic lineage.

Biomaterials Regulate Mechanosensors YAP/TAZ in Stem Cell Growth and Differentiation.

Tissue-resident stem cells are surrounded by a microenvironment known as 'stem cell niche' which is specific for each stem cell type. This niche comprises of cell-intrinsic and -extrinsic factors like biochemical and biophysical signals, which regulate stem cell characteristics and differentiation. Biochemical signals have been thoroughly studied however, the effect of biophysical signals on stem cell regulation is yet to be completely understood.

Pancreas development and the Polycomb group protein complexes.

The dual nature of pancreatic tissue permits both endocrine and exocrine functions. Enzymatic secretions by the exocrine pancreas help digestive processes while the pancreatic hormones regulate glucose homeostasis and energy metabolism. Pancreas organogenesis is defined by a conserved array of signaling pathways that act on common gut progenitors to bring about the generation of diverse cell types.

PRC1 catalytic unit RING1B regulates early neural differentiation of human pluripotent stem cells.

Background: Polycomb group (PcG) proteins are histone modifiers which control gene expression by assembling into large repressive complexes termed - Polycomb repressive complex (PRC); RING1B, core catalytic subunit of PRC1 that performs H2AK119 monoubiquitination leading to gene repression. The role of PRC1 complex during early neural specification in humans is unclear; we have tried to uncover the role of PRC1 in neuronal differentiation using human pluripotent stem cells as an in vitro model.

Results: We differentiated both human embryonic stem cells (hESCs) and human induced pluripotent stem cells (hiPSCs) towards neural progenitor stage evident from the expression of NESTIN, TUJ1, NCAD, and PAX6.

Clocking the circadian genes in human embryonic stem cells.

Multicellular organisms respond to changing environment which is primarily driven by light from the sun. Essential cyclical processes such as digestion, sleep, migration and breeding are controlled by set of genes know as circadian genes. The core circadian genes comprise of , , and that are expressed cyclically and they regulate expression of several genes downstream.

Inhibition of RING1B alters lineage specificity in human embryonic stem cells.

Polycomb group (PcG) proteins are histone modifiers which are known to perform transcriptional repression and have been shown to be critical during murine embryonic development. PcGs are broadly characterized into polycomb repressive complex 1 (PRC1) and 2 and (PRC2). RING1B, core catalytic unit of PRC1 performs H2AK119 monoubiquitination leading to transcriptional repression.

Polycomb repressive complex 1: Regulators of neurogenesis from embryonic to adult stage.

Development of vertebrate nervous system is a complex process which involves differential gene expression and disruptions in this process or in the mature brain, may lead to neurological disorders and diseases. Extensive work that spanned several decades using rodent models and recent work on stem cells have helped uncover the intricate process of neuronal differentiation and maturation. There are various morphological changes, genetic and epigenetic modifications which occur during normal mammalian neural development, one of the chromatin modifications that controls vital gene expression are the posttranslational modifications on histone proteins, that controls accessibility of translational machinery.

Anticancer activity of methylene blue via inhibition of heat shock protein 70.

Introduction: Heat shock protein 70 (Hsp70) and heat shock protein 90 (Hsp90) chaperones are indispensable to lung cancer cells for their survival and proliferation. In this study we evaluated and compared anticancer potential of methylene blue (MB) as an Hsp70 inhibitor, novobiocin (NB) a well-known Hsp90 inhibitor and their combination.

Methods: In vitro evaluation was done by cell viability assays, fluorescent staining, and flow cytometry analysis using A549 non-small cell lung cancer cells.

Genetic and Epigenetic Profiling Reveals EZH2-mediated Down Regulation of OCT-4 Involves NR2F2 during Cardiac Differentiation of Human Embryonic Stem Cells.

Human embryonic (hES) stem cells are widely used as an in vitro model to understand global genetic and epigenetic changes that occur during early embryonic development. In-house derived hES cells (KIND1) were subjected to directed differentiation into cardiovascular progenitors (D12) and beating cardiomyocytes (D20). Transcriptome profiling of undifferentiated (D0) and differentiated (D12 and 20) cells was undertaken by microarray analysis.

Lineage specific expression of Polycomb Group Proteins in human embryonic stem cells in vitro.

Human embryonic (hES) stem cells are an excellent model to study lineage specification and differentiation into various cell types. Differentiation necessitates repression of specific genes not required for a particular lineage. Polycomb Group (PcG) proteins are key histone modifiers, whose primary function is gene repression.

Polycomb group protein expression during differentiation of human embryonic stem cells into pancreatic lineage in vitro.

Background: Polycomb Group (PcG) proteins are chromatin modifiers involved in early embryonic development as well as in proliferation of adult stem cells and cancer cells. PcG proteins form large repressive complexes termed Polycomb Repressive Complexes (PRCs) of which PRC1 and PRC2 are well studied. Differentiation of human Embryonic Stem (hES) cells into insulin producing cells has been achieved to limited extent, but several aspects of differentiation remain unexplored.

Differentiation of human ES cell line KIND-2 to yield tripotent cardiovascular progenitors.

Human embryonic stem cells (hESCs) have the ability to differentiate into all the three lineages and are an ideal starting material to obtain cells of desired lineage for regenerative medicine. Continued efforts are needed to evolve more robust protocols to obtain cells of desired lineages and in larger numbers. Also, it has now been realized that rather than transplanting fully committed cells differentiated in vitro, it may be ideal to transplant committed progenitors which retain the intrinsic ability to proliferate and also differentiate better into multiple lineages based on the in vivo cues.