Integrated FGF and BMP signaling controls the progression of progenitor cell differentiation and the emergence of pattern in the embryonic anterior pituitary

Development ◽  
1998 ◽  
Vol 125 (6) ◽  
pp. 1005-1015 ◽  
Author(s):  
J. Ericson ◽  
S. Norlin ◽  
T.M. Jessell ◽  
T. Edlund
Keyword(s):  
Progenitor Cells ◽  
Anterior Pituitary ◽  
Progenitor Cell ◽  
Cell Types ◽  
Bmp Signaling ◽  
Cell Identity ◽  
Coordinate Control ◽  
Signaling Function ◽  
Proliferation And Differentiation

The mechanisms by which inductive signals control the identity, proliferation and timing of differentiation of progenitor cells in establishing spatial pattern in developing vertebrate tissues remain poorly understood. We have addressed this issue in the embryonic anterior pituitary, an organ in which distinct hormone cell types are generated in a precise temporal and spatial order from an apparently homogenous ectodermal primordium. We provide evidence that in this tissue the coordinate control of progenitor cell identity, proliferation and differentiation is imposed by spatial and temporal restrictions in FGF- and BMP-mediated signals. These signals derive from adjacent neural and mesenchymal signaling centers: the infundibulum and ventral juxtapituitary mesenchyme. The infundibulum appears to have a dual signaling function, serving initially as a source of BMP4 and subsequently of FGF8. The ventral juxtapituitary mesenchyme appears to serve as a later source of BMP2 and BMP7. In vitro, FGFs promote the proliferation of progenitor cells, prevent their exit from the cell cycle and contribute to the specification of progenitor cell identity. BMPs, in contrast, have no apparent effect on cell proliferation but instead appear to act with FGFs to control the initial selection of thyrotroph and corticotroph progenitor identity.

Regulation of the neural patterning activity of sonic hedgehog by secreted BMP inhibitors expressed by notochord and somites

Development ◽  
2000 ◽  
Vol 127 (22) ◽  
pp. 4855-4866 ◽  
Author(s):  
K.F. Liem ◽  
T.M. Jessell ◽  
J. Briscoe
Keyword(s):  
Neural Tube ◽  
Progenitor Cell ◽  
Cell Types ◽  
Neural Cell ◽  
Bmp Signaling ◽  
Neural Cells ◽  
Cell Identity ◽  
Neuronal Fate ◽  
Ventral Neural Tube

The secretion of Sonic hedgehog (Shh) from the notochord and floor plate appears to generate a ventral-to-dorsal gradient of Shh activity that directs progenitor cell identity and neuronal fate in the ventral neural tube. In principle, the establishment of this Shh activity gradient could be achieved through the graded distribution of the Shh protein itself, or could depend on additional cell surface or secreted proteins that modify the response of neural cells to Shh. Cells of the neural plate differentiate from a region of the ectoderm that has recently expressed high levels of BMPs, raising the possibility that prospective ventral neural cells are exposed to residual levels of BMP activity. We have examined whether modulation of the level of BMP signaling regulates neural cell responses to Shh, and thus might contribute to the patterning of cell types in the ventral neural tube. Using an in vitro assay of neural cell differentiation we show that BMP signaling markedly alters neural cell responses to Shh signals, eliciting a ventral-to-dorsal switch in progenitor cell identity and neuronal fate. BMP signaling is regulated by secreted inhibitory factors, including noggin and follistatin, both of which are expressed in or adjacent to the neural plate. Conversely, follistatin but not noggin produces a dorsal-to-ventral switch in progenitor cell identity and neuronal fate in response to Shh both in vitro and in vivo. These results suggest that the specification of ventral neural cell types depends on the integration of Shh and BMP signaling activities. The net level of BMP signaling within neural tissue may be regulated by follistatin and perhaps other BMP inhibitors secreted by mesodermal cell types that flank the ventral neural tube.

Development and regeneration in the central nervous system

1990 ◽  
Vol 327 (1239) ◽  
pp. 127-143 ◽  
Keyword(s):  
Stem Cells ◽  
Central Nervous System ◽  
Nervous System ◽  
Progenitor Cells ◽  
Progenitor Cell ◽  
Cell Types ◽  
The Central Nervous System

As part of our attempts to understand principles that underly organism development, we have been studying the development of the rat optic nerve. This simple tissue is composed of three glial cell types derived from two distinct cellular lineages. Type-1 astrocytes appear to be derived from a monopotential neuroepithelial precursor, whereas type-2 astrocytes and oligodendrocytes are derived from a common oligodendrocyte-type-2 astrocyte (O-2A) progenitor cell. Type-1 astrocytes modulate division and differentiation of O-2A progenitor cells through secretion of platelet-derived growth factor, and can themselves be stimulated to divide by peptide mitogens and through stimulation of neurotransmitter receptors. In vitro analysis indicates that many dividing O-2A progenitors derived from optic nerves of perinatal rats differentiate symmetrically and clonally to give rise to oligodendrocytes, or can be induced to differentiate into type-2 astrocytes. O-2A perinatal progenitors can also differentiate to form a further O-2A lineage cell, the O-2A adult progenitor, which has properties specialized for the physiological requirements of the adult nervous system. In particular, O-2A adult progenitors have many of the features of stem cells, in that they divide slowly and asymmetrically and appear to have the capacity for extended self-renewal. The apparent derivation of a slowly and asymmetrically dividing cell, with properties appropriate for homeostatic maintenance of existing populations in the mature animal, from a rapidly dividing cell with properties suitable for the rapid population and myelination of central nervous system (CNS) axon tracts during early development, offers novel and unexpected insights into the possible origin of self-renewing stem cells and also into the role that generation of stem cells may play in helping to terminate the explosive growth of embryogenesis. Moreover, the properties of O-2A adult progenitor cells are consistent with, and may explain, the failure of successful myelin repair in conditions such as multiple sclerosis, and thus seem to provide a cellular biological basis for understanding one of the key features of an important human disease.

Abstract 1964: Bone Morphogenetic Protein Antagonist “Protein Related to Dan and Cerberus” Promotes Differentiation of Embryonic Stem Cells to Atrial Cardiomyocytes

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Jingbo Yan ◽  
Jianyong Hu ◽  
Iris I Mueller ◽  
William H Heaton ◽  
Wan-Der Wang ◽  
...  
Keyword(s):  
Notch Signaling ◽  
Progenitor Cells ◽  
Molecular Mechanisms ◽  
Es Cells ◽  
Embryonic Stem ◽  
Cell Types ◽  
Bmp Signaling ◽  
Cardiac Differentiation ◽  
Cardiovascular Cells

The molecular factors that regulate cardiac differentiation have been extensively studied, yet, relatively little is known about how cardiomyocytes acquire atrial versus ventricular characteristics. Embryonic stem (ES) cells, which have the potential to differentiate to a wide array of distinct cell types, including most types of cardiovascular cells, offer a pertinent in vitro model to work out the molecular mechanisms of atrial specification and differentiation. We discovered that the secreted antagonist of BMP signaling, Protein Related to Dan and Cerberus (PRDC, also called Gremlin2) leads to a surge in cardiomyocytic differentiation when applied to mouse ES-derived cardiac progenitor cells. This property is unique to PRDC among tested BMP antagonists. Lineage expansion is restricted to cardiomyocytes, with the differentiation of endodermal, blood, endothelial and neuronal cells being unaffected. Using molecular and electrophysiological analyses, we show that PRDC-induced cardiomyocytes acquire atrial characteristics. Consistent with the in vitro results, we found that injection of PRDC mRNA into the developing zebrafish embryo leads to supernumerary contracting areas. The ectopic cardiomyocytes express atrial-, but not ventricular- specific cardiac genes. We determined that PRDC treatment induces the expression of COUP-TFII, a known transcriptional regulator of atrial differentiation, but suppresses Notch signaling. Inhibition of Notch is sufficient to induce atrial-specific genes; however, blocking Notch does not expand the cardiogenic fields. Taken together, our data suggest that antagonism of BMP and Notch signaling by PRDC is a critical early step in the specification, expansion and differentiation of atrial progenitor cells. This information might be relevant for treating atrial degeneration, as well as for understanding the etiology of atrial fibrillation.

scholarly journals The role of IGF1 on the differentiation of prolactin secreting cells in the mouse anterior pituitary

2009 ◽  
Vol 203 (2) ◽  
pp. 231-240 ◽  
Author(s):  
Tamiki Hikake ◽  
Shinji Hayashi ◽  
Taisen Iguchi ◽  
Tomomi Sato
Keyword(s):  
Cell Proliferation ◽  
Progenitor Cells ◽  
Anterior Pituitary ◽  
Cell Number ◽  
Postnatal Period ◽  
Gh Cells ◽  
Cell Proliferation And Differentiation ◽  
Proliferation And Differentiation

IGF1 knockout (IGF1KO) mice show a reduced number of prolactin (PRL) producing cells (PRL cells); however, the role of IGF1 in PRL cell proliferation and differentiation in immature mice is unclear. In this study, ontogenic changes in the percentages of PRL cells, GH producing cells (GH cells), and 5-bromo-2′-deoxyuridine (BrdU)-labeled cells in the anterior pituitary of male IGF1KO mice during the postnatal period were investigated. The percentage of PRL cells in IGF1KO mice was significantly lower at day 20 compared with that in wild-type (WT) mice, while GH cells in IGF1KO mice were significantly increased from day 10. From days 5 to 20, the percentage of BrdU-labeled cells in WT and IGF1KO mice was similar. PRL cells and GH cells are thought to originate from the same progenitor cells, therefore, PRL cells in IGF1KO mice are not able to differentiate because progenitor cells have already committed to be GH cells. However, IGF1, 17β-estradiol (E2), epidermal growth factor (EGF), or IGF1 plus E2 treatments increased the PRL cell number in the pituitaries in vitro of 10-day-old WT and IGF1KO mice. This fact suggests that these factors are involved in PRL cell proliferation and differentiation. In addition, the increase of PRL cells in IGF1KO mice stimulated by E2 or EGF was less than that of WT mice. Thus, IGF1 plays a crucial role in PRL cell proliferation and differentiation in mouse pituitaries by regulating the differentiation of progenitor cells and mediating the actions of E2 and EGF.

scholarly journals Microcarrier Screening and Evaluation for Dynamic Expansion of Human Periosteum-Derived Progenitor Cells in a Xenogeneic Free Medium

2021 ◽  
Vol 9 ◽  
Author(s):  
Kathleen Van Beylen ◽  
Ioannis Papantoniou ◽  
Jean-Marie Aerts
Keyword(s):  
Progenitor Cells ◽  
Cell Expansion ◽  
Progenitor Cell ◽  
Large Scale ◽  
Expansion Method ◽  
Cell Types ◽  
Free Medium ◽  
Efficient Expansion

An increasing need toward a more efficient expansion of adherent progenitor cell types arises with the advancements of cell therapy. The use of a dynamic expansion instead of a static planar expansion could be one way to tackle the challenges of expanding adherent cells at a large scale. Microcarriers are often reported as a biomaterial for culturing cells in suspension. However, the type of microcarrier has an effect on the cell expansion. In order to find an efficient expansion process for a specific adherent progenitor cell type, it is important to investigate the effect of the type of microcarrier on the cell expansion. Human periosteum-derived progenitor cells are extensively used in skeletal tissue engineering for the regeneration of bone defects. Therefore, we evaluated the use of different microcarriers on human periosteum-derived progenitor cells. In order to assess the potency, identity and viability of these cells after being cultured in the spinner flasks, this study performed several in vitro and in vivo analyses. The novelty of this work lies in the combination of screening different microcarriers for human periosteum-derived progenitor cells with in vivo assessments of the cells’ potency using the microcarrier that was selected as the most promising one. The results showed that expanding human periosteum-derived progenitor cells in spinner flasks using xeno-free medium and Star-Plus microcarriers, does not affect the potency, identity or viability of the cells. The potency of the cells was assured with an in vivo evaluation, where bone formation was achieved. In summary, this expansion method has the potential to be used for large scale cell expansion with clinical relevance.

scholarly journals From Cell States to Cell Fates: How Cell Proliferation and Neuronal Differentiation Are Coordinated During Embryonic Development

2022 ◽  
Vol 15 ◽  
Author(s):  
Carla Belmonte-Mateos ◽  
Cristina Pujades
Keyword(s):  
Progenitor Cells ◽  
Progenitor Cell ◽  
New Technologies ◽  
Cell Lineage ◽  
Cell Types ◽  
Lineage Tracing ◽  
Vertebrate Brain ◽  
Proliferation And Differentiation ◽  
Cell Diversity ◽  
The Right

The central nervous system (CNS) exhibits an extraordinary diversity of neurons, with the right cell types and proportions at the appropriate sites. Thus, to produce brains with specific size and cell composition, the rates of proliferation and differentiation must be tightly coordinated and balanced during development. Early on, proliferation dominates; later on, the growth rate almost ceases as more cells differentiate and exit the cell cycle. Generation of cell diversity and morphogenesis takes place concomitantly. In the vertebrate brain, this results in dramatic changes in the position of progenitor cells and their neuronal derivatives, whereas in the spinal cord morphogenetic changes are not so important because the structure mainly grows by increasing its volume. Morphogenesis is under control of specific genetic programs that coordinately unfold over time; however, little is known about how they operate and impact in the pools of progenitor cells in the CNS. Thus, the spatiotemporal coordination of these processes is fundamental for generating functional neuronal networks. Some key aims in developmental neurobiology are to determine how cell diversity arises from pluripotent progenitor cells, and how the progenitor potential changes upon time. In this review, we will share our view on how the advance of new technologies provides novel data that challenge some of the current hypothesis. We will cover some of the latest studies on cell lineage tracing and clonal analyses addressing the role of distinct progenitor cell division modes in balancing the rate of proliferation and differentiation during brain morphogenesis. We will discuss different hypothesis proposed to explain how progenitor cell diversity is generated and how they challenged prevailing concepts and raised new questions.

scholarly journals Cell Sources for Human In vitro Bone Models

2021 ◽  
Author(s):  
Sana Ansari ◽  
Keita Ito ◽  
Sandra Hofmann
Keyword(s):  
Bone Marrow ◽  
Progenitor Cells ◽  
Peripheral Blood ◽  
Cell Types ◽  
Medium Composition ◽  
Differentiation Potential ◽  
Osteoclast Progenitor ◽  
Proliferation And Differentiation ◽  
Cell Sources

Abstract Purpose of Review One aim in bone tissue engineering is to develop human cell-based, 3D in vitro bone models to study bone physiology and pathology. Due to the heterogeneity of cells among patients, patient’s own cells are needed to be obtained, ideally, from one single cell source. This review attempts to identify the appropriate cell sources for development of such models. Recent Findings Bone marrow and peripheral blood are considered as suitable sources for extraction of osteoblast/osteocyte and osteoclast progenitor cells. Recent studies on these cell sources have shown no significant differences between isolated progenitor cells. However, various parameters such as medium composition affect the cell’s proliferation and differentiation potential which could make the peripheral blood-derived stem cells superior to the ones from bone marrow. Summary Peripheral blood can be considered a suitable source for osteoblast/osteocyte and osteoclast progenitor cells, being less invasive for the patient. However, more investigations are needed focusing on extraction and differentiation of both cell types from the same donor sample of peripheral blood.

scholarly journals Nitric Oxide Dependent Metabolism Regulates the Proliferation and Differentiation of Stress Erythroid Progenitors

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 921-921
Author(s):  
Baiye Ruan ◽  
Yuanting Chen ◽  
Imhoi Koo ◽  
Jingwei Cai ◽  
John Mcguigan ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Steady State ◽  
Progenitor Cells ◽  
Progenitor Cell ◽  
Erythroid Differentiation ◽  
No Production ◽  
Erythroid Progenitors ◽  
Stress Erythropoiesis ◽  
Proliferation And Differentiation

Abstract Infection and tissue damage induce inflammation, which increases myelopoiesis at the expense of steady state erythropoiesis. Stress erythropoiesis is induced to compensate for the loss of erythroid output until the inflammation is resolved and bone marrow erythropoiesis can resume. Steady state erythropoiesis constantly produces erythrocytes, while stress erythropoiesis generates a bolus of new erythrocytes through the rapid expansion of immature progenitor cells which is followed by the synchronous differentiation of progenitors. We hypothesized that the proliferation of early progenitor cells and their transition to differentiation is regulated by changes in metabolism. Metabolomics and isotope tracing analysis was performed to assess the intracellular metabolic profiles in proliferating progenitors isolated from in vitro stress erythropoiesis cultures. We observed an active engagement of glucose metabolism in glycolysis and anabolic biosynthesis, while the levels of TCA intermediates suggested that TCA cycle and mitochondrial respiration were blocked. Concomitantly, inducible nitric oxide synthase (iNOS) was induced in progenitor cells to increase the production of nitric oxide (NO), which was demonstrated to be crucial for proliferating progenitor metabolism. Inhibition or genetic mutation of iNOS decreased NO levels resulting in the suppression of progenitor proliferation in vitro and in vivo. As evaluated by RNA-seq, inhibition of iNOS suppressed cell proliferation-related pathways including cell cycle and nucleotide metabolism, while upregulating erythroid differentiation genes. These data suggest that iNOS-derived NO production establishes a metabolism that promotes the proliferation of progenitor cells while inhibiting their differentiation. Notably, proliferating progenitor cells displayed low levels of the metabolite itaconate and decreased expression of Immunoresponsive gene 1 (Irg1), the enzyme that catalyzes itaconate synthesis from cis-aconitate. Further analysis showed that the addition of 4-Octyl itaconate (OI), a cell-permeable itaconate derivative, inhibited iNOS-derived NO production by activating nuclear factor erythroid 2-related factor 2 (Nrf2), which in turn impaired progenitor expansion. These results indicate that itaconate production is inhibited to enable the accumulation of NO and the NO dependent metabolism required for progenitor cell proliferation during the initial expansion stage of stress erythropoiesis. In contrast, the transition to differentiation is marked by elevated itaconate synthesis, Nrf2 activation, and attenuated iNOS expression. We hypothesized that the inhibition of NO production alters metabolism and in concert with new cell signaling removes the NO-dependent inhibition of erythroid program, which allows the differentiation of progenitor cells. We tested this mechanism by examining the effects of iNOS inhibitors and mutants in iNOS, Irg1 and Nrf2 on progenitor cells isolated from differentiation cultures. iNOS deficiency led to the activation of erythroid transcriptional program, and increased numbers of mature progenitors as well as stress BFU-Es. In contrast, Irg1 and Nrf2 mutants showed impaired transition to erythroid differentiation, while they had elevated iNOS expression and NO production. Further analysis showed that treatment with either OI or iNOS inhibitor inhibited NO production in Irg1 and Nrf2 deficient progenitors, and consequently rescued the defects in erythroid differentiation. These data support a model in which inflammation inhibits steady state erythropoiesis, while at the same time promoting stress erythropoiesis to maintain homeostasis. Our work reveals a dynamic and tight coordination between pro-inflammatory signals and progenitor cell metabolism in regulating the proliferation and differentiation of stress erythroid progenitors, and highlights the therapeutic potential of targeting metabolic and inflammatory signaling pathways in inflammatory anemia. Disclosures Paulson: Forma Therapeutics: Consultancy.

Bone Marrow Niches for Skeletal Progenitor Cells and their Inhabitants in Health and Disease

2019 ◽  
Vol 14 (4) ◽  
pp. 305-319 ◽  
Author(s):  
Marietta Herrmann ◽  
Franz Jakob
Keyword(s):  
Bone Marrow ◽  
Progenitor Cells ◽  
Progenitor Cell ◽  
Adult Stem Cells ◽  
Current Knowledge ◽  
Cell Populations ◽  
Surface Markers ◽  
Bone Marrow Niches

The bone marrow hosts skeletal progenitor cells which have most widely been referred to as Mesenchymal Stem or Stromal Cells (MSCs), a heterogeneous population of adult stem cells possessing the potential for self-renewal and multilineage differentiation. A consensus agreement on minimal criteria has been suggested to define MSCs in vitro, including adhesion to plastic, expression of typical surface markers and the ability to differentiate towards the adipogenic, osteogenic and chondrogenic lineages but they are critically discussed since the differentiation capability of cells could not always be confirmed by stringent assays in vivo. However, these in vitro characteristics have led to the notion that progenitor cell populations, similar to MSCs in bone marrow, reside in various tissues. MSCs are in the focus of numerous (pre)clinical studies on tissue regeneration and repair.Recent advances in terms of genetic animal models enabled a couple of studies targeting skeletal progenitor cells in vivo. Accordingly, different skeletal progenitor cell populations could be identified by the expression of surface markers including nestin and leptin receptor. While there are still issues with the identity of, and the overlap between different cell populations, these studies suggested that specific microenvironments, referred to as niches, host and maintain skeletal progenitor cells in the bone marrow. Dynamic mutual interactions through biological and physical cues between niche constituting cells and niche inhabitants control dormancy, symmetric and asymmetric cell division and lineage commitment. Niche constituting cells, inhabitant cells and their extracellular matrix are subject to influences of aging and disease e.g. via cellular modulators. Protective niches can be hijacked and abused by metastasizing tumor cells, and may even be adapted via mutual education. Here, we summarize the current knowledge on bone marrow skeletal progenitor cell niches in physiology and pathophysiology. We discuss the plasticity and dynamics of bone marrow niches as well as future perspectives of targeting niches for therapeutic strategies.

Sign in / Sign up

Export Citation Format

Share Document