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Stem Cell Differentiation (stem + cell_differentiation)

Distribution by Scientific Domains

Life Sciences	47%
Medical Sciences	42%
Chemistry	10%

Selected Abstracts

Modular Peptide Growth Factors for Substrate-Mediated Stem Cell Differentiation,

ANGEWANDTE CHEMIE, Issue 34 2009
Sam Lee Dr.
Die Sequenzspezifität beim Binden eines modularen Peptidwachstumsfaktors (eBGa3) mit einer von BMP2 abgeleiteten Sequenz und einer durch Osteocalcin inspirierten Mineralbindesequenz an Ca-Ionen von Hydroxyapatit (HA) ist vermutlich teilweise auf die Entwicklung einer ,-helicalen Struktur in Gegenwart von HA zurückzuführen, durch die ,-carboxylierte Glutaminsäurereste im Peptid (cyan) von Ca-Atomen (orange) im HA-Kristallgitter registriert werden können. [source]

Regulation of Human Skeletal Stem Cells Differentiation by Dlk1/Pref-1

JOURNAL OF BONE AND MINERAL RESEARCH, Issue 5 2004
Basem M Abdallah
Abstract Dlk-1/Pref-1 was identified as a novel regulator of human skeletal stem cell differentiation. Dlk1/Pref-1 is expressed in bone and cultured osteoblasts, and its constitutive overexpression led to inhibition of osteoblast and adipocyte differentiation of human marrow stromal cells. Introduction: Molecular control of human mesenchymal stem cell (hMSC) differentiation into osteoblasts and adipocytes is not known. In this study, we examined the role of delta-like 1/preadipocyte factor-1 (Dlk1/Pref-1) in regulating the differentiation of hMSCs. Materials and Methods: As a model for hMSCs, we have stably transduced telomerase-immortalized hMSC (hMSC-TERT) with the full length of human Dlk1/Pref-1 cDNA and tested its effect on hMSC growth and differentiation into osteoblasts or adipocytes as assessed by cytochemical staining, FACS analysis, and real time PCR. Ex vivo calvaria organ cultures assay was used to confirm the in vitro effect of Dlk/Pref-1 on bone formation. Results: Dlk1/Pref-1 was found to be expressed in fetal and adult bone, hMSCs, and some osteoblastic cell lines. A retroviral vector containing the human Dlk1/Pref-1 cDNA was used to create a cell line (hMSC-dlk1) expressing high levels of Dlk1/Pref-1 protein. Overexpression of Dlk1/Pref-1 did not affect the proliferation rate of hMSC, but the ability to form mature adipocytes, mineralized matrix in vitro, and new bone formation in neonatal murine calvariae organ cultures was reduced. These effects were associated with inhibition of gene expression markers of late stages of adipocyte (adipocyte fatty acid-binding protein [aP2], peroxisome proliferator-activated receptor-gamma2 [PPAR,2], and adiponectin [APM1]) and osteoblast differentiation (alkaline phosphatase [ALP], collagen type I [Col1], and osteocalcin [OC]). Lineage commitment markers for adipocytes (adipocyte determination and differentiation factor ,1 [ADD1]) and osteoblasts (core binding factor/runt-related binding factor 2 [Cbfa1/Runx2]) were not affected. Conclusion: During hMSC differentiation, Dlk1/Pref-1 maintains the size of the bipotential progenitor cell pool by inhibiting the formation of mature osteoblasts and adipocytes. [source]

Epigenetic regulation in neural stem cell differentiation

DEVELOPMENT GROWTH & DIFFERENTIATION, Issue 6 2010
Berry Juliandi
The central nervous system (CNS) is composed of three major cell types , neurons, astrocytes, and oligodendrocytes , which differentiate from common multipotent neural stem cells (NSCs). This differentiation process is regulated spatiotemporally during the course of mammalian development. It is becoming apparent that epigenetic regulation is an important cell-intrinsic program, which can interact with transcription factors and environmental cues to modulate the differentiation of NSCs. This knowledge is important given the potential of NSCs to produce specific CNS cell types that will be beneficial for clinical applications. Here we review recent findings that address molecular mechanisms of epigenetic and transcription factor-mediated regulation that specify NSC fate during CNS development, with a particular focus on the developing mammalian forebrain. [source]

Analysis of human muscle stem cells reveals a differentiation-resistant progenitor cell population expressing Pax7 capable of self-renewal

DEVELOPMENTAL DYNAMICS, Issue 1 2009
Bradley Pawlikowski
Abstract Studies using mouse models have established a critical role for resident satellite stem cells in skeletal muscle development and regeneration, but little is known about this paradigm in human muscle. Here, using human muscle stem cells, we address their lineage progression, differentiation, migration, and self-renewal. Isolated human satellite cells expressed ,7-integrin and other definitive muscle markers, were highly motile on laminin substrates and could undergo efficient myotube differentiation and myofibrillogenesis. However, only a subpopulation of the myoblasts expressed Pax7 and displayed a variable lineage progression as measured by desmin and MyoD expression. Analysis identified a differentiation-resistant progenitor cell population that was Pax7+/desmin, and capable of self-renewal. This study extends our understanding of the role of Pax7 in regulating human satellite stem cell differentiation and self-renewal. Developmental Dynamics 238:138,149, 2009. © 2008 Wiley-Liss, Inc. [source]

Regulation of Human Skeletal Stem Cells Differentiation by Dlk1/Pref-1

Osteoclastogenesis, Bone Resorption, and Osteoclast-Based Therapeutics

JOURNAL OF BONE AND MINERAL RESEARCH, Issue 4 2003
Mone Zaidi
Abstract Over the past decade, advances in molecular tools, stem cell differentiation, osteoclast and osteoblast signaling mechanisms, and genetically manipulated mice models have resulted in major breakthroughs in understanding osteoclast biology. This review focuses on key advances in our understanding of molecular mechanisms underlying the formation, function, and survival of osteoclasts. These include key signals mediating osteoclast differentiation, including PU.1, RANK, CSF-1/c-fms, and src, and key specializations of the osteoclast including HCl secretion driven by H+ -ATPase and the secretion of collagenolytic enzymes including cathepsin K and matrix metalloproteinases (MMPs). These pathways and highly expressed proteins provide targets for specific therapies to modify bone degradation. The main outstanding issues, basic and translational, will be considered in relation to the osteoclast as a target for antiresorptive therapies. [source]

Cell-to-cell cross-talk between mesenchymal stem cells and cardiomyocytes in co-culture

JOURNAL OF CELLULAR AND MOLECULAR MEDICINE, Issue 5a 2008
E. Y. Plotnikov
Abstract The goals of the study were: (1) to explore the communication between human mesenchymal stem cells (MSC) and rat cardiac myocytes resulting in differentiation of the stem cells and, (2) to evaluate the role of mitochondria in it. Light and fluorescence microscopy as well as scanning electron microscopy revealed that after co-cultivation, cells formed intercellular contacts and transient exchange with cytosolic elements could be observed. The transport of cytosolic entity had no specific direction. Noticeably, mitochondria also could be transferred to the recipient cells in a unidirectional fashion (towards cardiomyocytes only). Transmission electron microscopy revealed significant variability in both the diameter of intercellular contacting tubes and their shape. Inside of these nanotubes mitochondria-resembling structures were identified. Moreover, after co-cultivation with cardiomyocytes, expression of human-specific myosin was revealed in MSC. Thus, we speculate that: (1) transport of intracellular elements to MSC possibly can determine the direction of their differentiation and, (2) mitochondria may be involved in the mechanism of the stem cell differentiation. It looks plausible that mitochondrial transfer to recipient cardiomyocytes may be involved in the mechanism of failed myocardium repair after stem cells transplantation. [source]

Nanoparticles as tools to study and control stem cells

JOURNAL OF CELLULAR BIOCHEMISTRY, Issue 4 2009
L. Ferreira
Abstract The use of nanoparticles in stem cell research is relatively recent, although very significant in the last 5 years with the publication of about 400 papers. The recent advances in the preparation of some nanomaterials, growing awareness of material science and tissue engineering researchers regarding the potential of stem cells for regenerative medicine, and advances in stem cell biology have contributed towards the boost of this research field in the last few years. Most of the research has been focused in the development of new nanoparticles for stem cell imaging; however, these nanoparticles have several potential applications such as intracellular drug carriers to control stem cell differentiation and biosensors to monitor in real time the intracellular levels of relevant biomolecules/enzymes. This review examines recent advances in the use of nanoparticles for stem cell tracking, differentiation and biosensing. We further discuss their utility and the potential concerns regarding their cytotoxicity. J. Cell. Biochem. 108: 746,752, 2009. © 2009 Wiley-Liss, Inc. [source]

A role for the Werner syndrome protein in epigenetic inactivation of the pluripotency factor Oct4

AGING CELL, Issue 4 2010
Johanna A. Smith
Summary Werner syndrome (WS) is an autosomal recessive disorder, the hallmarks of which are premature aging and early onset of neoplastic diseases (Orren, 2006; Bohr, 2008). The gene, whose mutation underlies the WS phenotype, is called WRN. The protein encoded by the WRN gene, WRNp, has DNA helicase activity (Gray et al., 1997; Orren, 2006; Bohr, 2008; Opresko, 2008). Extensive evidence suggests that WRNp plays a role in DNA replication and DNA repair (Chen et al., 2003; Hickson, 2003; Orren, 2006; Turaga et al., 2007; Bohr, 2008). However, WRNp function is not yet fully understood. In this study, we show that WRNp is involved in de novo DNA methylation of the promoter of the Oct4 gene, which encodes a crucial stem cell transcription factor. We demonstrate that WRNp localizes to the Oct4 promoter during retinoic acid-induced differentiation of human pluripotent cells and associates with the de novo methyltransferase Dnmt3b in the chromatin of differentiating pluripotent cells. Depletion of WRNp does not affect demethylation of lysine 4 of the histone H3 at the Oct4 promoter, nor methylation of lysine 9 of H3, but it blocks the recruitment of Dnmt3b to the promoter and results in the reduced methylation of CpG sites within the Oct4 promoter. The lack of DNA methylation was associated with continued, albeit greatly reduced, Oct4 expression in WRN-deficient, retinoic acid-treated cells, which resulted in attenuated differentiation. The presented results reveal a novel function of WRNp and demonstrate that WRNp controls a key step in pluripotent stem cell differentiation. [source]

Stem Cell Review Series: Regulating highly potent stem cells in aging: environmental influences on plasticity

AGING CELL, Issue 4 2008
Jay M. Edelberg
Summary Significant advances in the past decade have revealed that a large number of highly plastic stem cells are maintained in humans through adulthood and are present even in older adults. These findings are notable in light of the reduced capacity for repair and regeneration in older tissues. The apparent dichotomy can be reconciled through an appreciation of the age-associated changes in the microenvironmental pathways that govern adult stem cell plasticity and differentiation patterns. Specifically, the recent identification of the age-related loss of the local platelet-derived growth factor signals that promote the induction of cardiac myocytes from Oct-3/4+ bone marrow stem cells, rather than impairment in the stem cells themselves, provides a template for understanding and targeting the environmental pathways underlying the regenerative capacity of older tissues and organs. It is projected that this paradigm extends to the overall regulation of adult stem cell biology, shifting the balance from tissue generation during development and maturation to the prevention of untoward stem cell differentiation with aging. [source]

Effects of delayed stabilization on fracture healing

JOURNAL OF ORTHOPAEDIC RESEARCH, Issue 12 2007
Theodore Miclau
Abstract Previous studies have revealed that delayed internal fixation can stimulate fracture callus formation and decrease the rate of nonunion. However, the effect of delayed stabilization on stem cell differentiation is unknown. To address this, we created fractures in mouse tibiae and applied external fixation immediately, at 24, 48, 72, or 96 h after injury. Fracture healing was analyzed at 10 days by histological methods for callus, bone, and cartilage formation, and the mechanical properties of the calluses were assessed at 14 days postinjury by tension testing. The results demonstrate that delaying stabilization for 24,96 h does not significantly affect the volume of the callus tissue (TV) and the new bone (BV) that formed by 10 days, or the mechanical properties of the calluses at 14 days, compared to immediate stabilization. However, delaying stabilization for 24,96 h induces 10,40× more cartilage in the fracture calluses compared with fractures stabilized immediately. These findings suggest that delaying stabilization during the early phase of fracture healing may not significantly stimulate bone repair, but may alter the mode of bone repair by directing formation of more cartilage. Fractures that are not rigidly stabilized form a significantly larger amount of callus tissue and cartilage by 10 days postinjury than fractures stabilized at 24,96 h, indicating that mechanical instability influences chondrocytes beyond the first 96 h of fracture healing. © 2007 Orthopaedic Research Society. © 2007 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 25:1552,1558, 2007 [source]

Induction of umbilical cord blood,derived ,2m,c-Met+ cells into hepatocyte-like cells by coculture with CFSC/HGF cells

LIVER TRANSPLANTATION, Issue 6 2005
Yunfang Wang
Several studies have indicated that adult stem cells derived from bone marrow (BM) and cord blood (CB) can differentiate into hepatocyte-like cells. This ability is important for the treatment of hepatic diseases with BM or CB as a potential approach. However, methods are still being developed for the efficient induction of stem cell differentiation and expansion to get enough cells to be useful. In the present study, we enriched a subset of umbilical cord blood ,2m,c-Met+ cells (UCBCCs) and investigated the combination effect of liver nonparenchymal cells (cirrhotic fat-storing cells [CFSCs]) and hepatocyte growth factor (HGF) on the induction of UCBCCs into hepatocyte-like cells. UCBCCs were cocultured with CFSC/HGF feeder layers either directly or separately using insert wells. Flow cytometric analysis showed that most UCBCCs were CD34+/,CD90+/,CD49f+CD29+Alb+AFP+. After cocultured with transgenic feeder layers for 7 days, UCBCCs displayed some morphologic characteristics of hepatocytes. Reverse-transcription polymerase chain reaction (RT-PCR) and immunofluorescence cell staining proved that the induced UCBCCs expressed several hepatocyte specific genes including AFP, Alb, CYP1B1 and cytokeratins CK18 and CK19. Furthermore, the induced cells displayed liver specific functions of indocyanine green (ICG) uptake, ammonium metabolism and albumin secretion. Hence, our data have demonstrated that UCBCCs might represent a novel subpopulation of CB-derived stem/progenitor cells capable of successful differentiation into hepatocyte-like cells when incubated with CFSC/HGF cells. In conclusion, not only HGF but also CFSCs and/or the secreted extracellular matrix (ECM) have been shown to be able to serve as essential microenvironment for hepatocyte differentiation. (Liver Transpl 2005;11:635,643.) [source]

Adult neural stem cells and their role in brain pathology,

THE JOURNAL OF PATHOLOGY, Issue 2 2009
G Yadirgi
Abstract Stem cells are multipotent cells that can give rise to a differentiated progeny as well as self-renew. The balanced coordination of these two stem cell fates is essential for embryonic development and tissue homeostasis in the adult. Perturbed stem cell function contributes significantly to a variety of pathological conditions, eg impaired self-renewal capacity due to cellular senescence contributes to ageing, and degenerative diseases or impaired stem cell differentiation by oncogenic mutations contribute to cancer formation. This review focuses on the molecular mechanisms involved in regulating the normal function of neural stem cells in the adult mammalian brain and on the involvement of these cells in brain pathology. Copyright © 2008 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. [source]

Rejection Reversibly Alters Enteroendocrine Cell Renewal in the Transplanted Small Intestine

AMERICAN JOURNAL OF TRANSPLANTATION, Issue 7 2009
T. M. Fishbein
Acute small intestinal allograft rejection presents clinically as an abrupt increase in ileal fluid output in the absence of extensive inflammation. We questioned whether acute intestinal rejection might be accompanied by a disturbance of normal intestinal stem cell differentiation. We examined the intestinal epithelial secretory cell lineage among patients experiencing early rejection before and during rejection as well as following corrective therapy. Lineage-specific progenitors were identified by their expression of stage-specific transcription factors. Progenitors of the enteroendocrine cell (EEC) expressing neurogenin-3 (NEUROG3) were found to be disproportionately reduced in numbers, along with their more mature EEC derivatives expressing neuro D; the enteric hormone PYY was the most profoundly depleted of all the EEC products evaluated. No change in the numbers of goblet or Paneth cells was observed. Steroid treatment resulted in resolution of clinical symptoms, restoration of normal patterns of EEC differentiation and recovery of normal levels of enteric hormones. Acute intestinal rejection is associated with a loss of certain subtypes of EEC, most profoundly, those expressing PYY. Deficiency of the mature EECs appears to occur as a consequence of a mechanism that depletes NEUROG3 EEC progenitors. Our study highlights the dynamics of the EEC lineage during acute intestinal rejection. [source]

Factors affecting proliferation and differentiation of lepidopteran midgut stem cells,

ARCHIVES OF INSECT BIOCHEMISTRY AND PHYSIOLOGY (ELECTRONIC), Issue 1 2010
Marcia J. Loeb
Midgut stem cells of last instar larvae and pupae of Heliothis virescens, Lymantria dispar and several other Lepidopteran species have been cultured in vitro and have been induced to proliferate using low titers of ecdysteroids and the 77-Kda peptide fragment, ,-arylphorin, isolated and identified from pupal fat body tissue. The insulin-related hormone, Bombyxin, also induced mitosis in cultured midgut stem cells; it appeared to be fast-acting and quickly inactivated, while ,-arylphorin was slower to act and had a longer lasting effect in vitro, indicating different functions for these proliferation agents. Changes in Calcium ion concentration within or outside the cells discretely affected stem cell differentiation, indicating a role for second messenger participation in peptide regulation of this process. Four different peptides (MDFs 1,4) that induced midgut stem cells to differentiate to mature midgut cell types in vitro were isolated and characterized from conditioned media and hemolymph of H. virescens and L. dispar. However, platelet-derived growth factor (PDGF), epidermal growth factor (EGF), and all-trans retinoic acid (RA) from vertebrate sources induced differentiation to non-midgut cell types as well. MDF1 was located in basal areas of columnar cells of midgut epithelium, although MDF2 was observed in all of the cytoplasm of columnar cells and in droplets of antibody positive material in the midgut lumen, suggesting a digestive function as well for this peptide. Anti-MDF-3 stained the central areas of cultured midgut columnar cells and the bases of columnar cells of midgut epithelium in vivo. Midgut secretory cells stained with anti-MDF-4; streams of MFD-4-positive material were observed extending from secretory cells facing the epithelial lumen, and as a layer on the hemolymph-facing side, suggesting an endocrine or paracrine function for this or an immunologically similar peptide. Published 2010 Wiley Periodicals, Inc. [source]

An efficient experimental strategy for mouse embryonic stem cell differentiation and separation of a cytokeratin-19-positive population of insulin-producing cells

CELL PROLIFERATION, Issue 4 2008
O. Naujok
Objectives: Embryonic stem cells are a potential source for insulin-producing cells, but existing differentiation protocols are of limited efficiency. Here, the aim has been to develop a new one, which drives development of embryonic stem cells towards insulin-producing cells rather than to neuronal cell types, and to combine this with a strategy for their separation from insulin-negative cells. Materials and methods: The cytokeratin-19 (CK19) promoter was used to control the expression of enhanced yellow fluorescence protein in mouse embryonic stem cells during their differentiation towards insulin-producing cells, using a new optimized four-stage protocol. Two cell populations, CK19+ and CK19, cells, were successfully fluorescence sorted and analysed. Results: The new method reduced neuronal progeny and suppressed differentiation into glucagon- and somatostatin-producing cells. Concomitantly, ,-cell like characteristics of insulin-producing cells were strengthened, as documented by high gene expression of the Glut2 glucose transporter and the transcription factor Pdx1. This novel protocol was combined with a cell-sorting technique. Through the combined procedure, a fraction of glucose-responsive insulin-secreting CK19+ cells was obtained with 40-fold higher insulin gene expression and 50-fold higher insulin content than CK19, cells. CK19+ cells were immunoreactive for C-peptide and had ultrastructural characteristics of an insulin-secretory cell. Conclusion: Differentiated CK19+ cells reflect an endocrine precursor cell type of ductal origin, potentially suitable for insulin replacement therapy in diabetes. [source]

New blood for hemoglobin in the lens: roles in stem cell differentiation and fibre cell organelle loss?

ACTA OPHTHALMOLOGICA, Issue 2008
MA WRIDE
Purpose Evidence is emerging for haemoglobin (Hb) expression outside the vascular system. We previously demonstrated Hb expression in the mouse lens during post-natal development and cataract progression. Here, we extended this work by carrying out a comprehensive spatio-temporal analysis of Hb subunit expression during mouse lens development and maturation. Methods We used RT-PCR, Western blotting and immunofluorescence to analyze Hb expression in mouse eyes (E16.5 to 9 wks). We also used a sensitive heme assay to test for the presence of heme in the lens by colourimetric assay and histological staining of paraffin-embedded sections. Results Hb subunits were expressed in lens epithelial cells and cortical lens fibre cells. However, the heme assay revealed negligible levels of this prosthetic group in the lens. Hb immunofluorescence was also observed in other regions of the developing eye including the cornea, the retinal ganglion cell layer and the retinal pigment epithelium. Finally, we also observed Hb expression in early embryos by microarray and during differentiation of embryonic stem (ES) cells into embryoid bodies (EBs) in vitro. Conclusion These results suggest a paradigm shift: Hb subunits are expressed in the eye during development and in the adult and, therefore, may have novel roles in ocular development, physiology and pathophysiology. The absence of heme from the lens indicates that at least some of these functions may be independent of oxygen metabolism. The pattern of expression of Hb in lens epithelial cells and cortical lens fibre cells may indicate an involvement for Hb subunits in lens epithelial cell differentiation into lens fibre cells and/or lens fibre cell organelle loss. [source]

Pluripotent plasticity of stem cells and liver repopulation

CELL BIOCHEMISTRY AND FUNCTION, Issue 3 2010
Luisa Gennero
Abstract Different types of stem cells have a role in liver regeneration or fibrous repair during and after several liver diseases. Otherwise, the origin of hepatic and/or extra-hepatic stem cells in reactive liver repopulation is under controversy. The ability of the human body to self-repair and replace the cells and tissues of some organs is often evident. It has been estimated that complete renewal of liver tissue takes place in about a year. Replacement of lost liver tissues is accomplished by proliferation of mature hepatocytes, hepatic oval stem cells differentiation, and sinusoidal cells as support. Hepatic oval cells display a distinct phenotype and have been shown to be a bipotential progenitor of two types of epithelial cells found in the liver, hepatocytes, and bile ductular cells. In gastroenterology and hepatology, the first attempts to translate stem cell basic research into novel therapeutic strategies have been made for the treatment of several disorders, such as inflammatory bowel diseases, diabetes mellitus, celiachy, and acute or chronic hepatopaties. In the future, pluripotent plasticity of stem cells will open a variety of clinical application strategies for the treatment of tissue injuries, degenerated organs. The promise of liver stem cells lie in their potential to provide a continuous and readily available source of liver cells that can be used for gene therapy, cell transplant, bio-artificial liver-assisted devices, drug toxicology testing, and use as an in vitro model to understand the developmental biology of the liver. Copyright © 2010 John Wiley & Sons, Ltd. [source]

Periodically Discontinuous Induction of Bone Marrow Stem Cells toward Osteogenic Differentiation in Vitro

BIOTECHNOLOGY PROGRESS, Issue 3 2008
Zhen Wang
This paper reveals that a discontinuous in vitro induction, namely, the periodic presence and absence of foreign induction factors, might be, under a certain condition, more effective to stimulate stem cells' differentiation than a continuous induction. Bone marrow stem cells (BMSCs) derived from Sprague Dawley rats were employed to examine the effects of discontinuous additions of osteogenic supplements with a series of alternate frequency in contrast to those with continuous induction or no induction. The results demonstrated that a suitable discontinuous induction was more able to achieve osteogenesis than not only no induction but also the associated continuous induction. Additionally, the osteogenic supplements were confirmed to enhance cell differentiation but suppress cell proliferation. So, the combination of differentiation extent per cell and cell number accounts for the "unexpected" good osteogenic effect of the discontinuous induction. The induction effect was found to be dependent upon alternate frequency, and the optimum alternate period in our experimental systems was determined to be around 4 days. Since it is very common to change culture medium every 2,4 days, such a strategy of discontinuous induction does not bring any extra manual work but reduces the consumption of foreign induction factors and significantly enhances the global differentiation efficacy. Our work thus affords a convenient and practical approach to achieve differentiation of BMSCs, which might be useful for potential large-scale culture and differentiation of stem cells. Meanwhile, the existence of optimum frequency implies some unknown inherent rhythms of cell proliferation and differentiation. [source]