AN INTRODUCTION TO STEM AND PROGENITOR CELL BIOLOGY

Regeneration of complex structures after injury requires dramatic changes in cellular behavior. Regenerating tissues initiate a program that includes diverse processes such as wound healing, cell death, dedifferentiation, and stem (or progenitor) cell proliferation; furthermore, newly regenerated tissues must integrate polarity and positional identity cues with preexisting body structures. Gene knockdown approaches and transgenesis-based lineage and functional analyses have been instrumental in deciphering various aspects of regenerative processes in diverse animal models for studying regeneration.

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Pivotal Role of Lnk Adaptor Protein in Endothelial Progenitor Cell Biology for Vascular Regeneration

Circulation Research ◽

10.1161/circresaha.108.192856 ◽

2009 ◽

Vol 104 (8) ◽

pp. 969-977 ◽

Cited By ~ 40

Author(s):

Sang-Mo Kwon ◽

Takahiro Suzuki ◽

Atsuhiko Kawamoto ◽

Masaaki Ii ◽

Masamichi Eguchi ◽

...

Keyword(s):

Endothelial Progenitor Cell ◽

Cell Biology ◽

Progenitor Cell ◽

Adaptor Protein ◽

Pivotal Role ◽

Endothelial Progenitor ◽

Vascular Regeneration

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Intersections of lung progenitor cells, lung disease and lung cancer

European Respiratory Review ◽

10.1183/16000617.0054-2017 ◽

2017 ◽

Vol 26 (144) ◽

pp. 170054 ◽

Cited By ~ 7

Author(s):

Carla F. Kim

Keyword(s):

Lung Cancer ◽

Progenitor Cells ◽

Cell Biology ◽

Progenitor Cell ◽

Genetically Engineered ◽

Response To Therapy ◽

Culture Techniques ◽

Genetically Engineered Mouse Models ◽

Approaches To Study ◽

Lung Progenitor

The use of stem cell biology approaches to study adult lung progenitor cells and lung cancer has brought a variety of new techniques to the field of lung biology and has elucidated new pathways that may be therapeutic targets in lung cancer. Recent results have begun to identify the ways in which different cell populations interact to regulate progenitor activity, and this has implications for the interventions that are possible in cancer and in a variety of lung diseases. Today's better understanding of the mechanisms that regulate lung progenitor cell self-renewal and differentiation, including understanding how multiple epigenetic factors affect lung injury repair, holds the promise for future better treatments for lung cancer and for optimising the response to therapy in lung cancer. Working between platforms in sophisticated organoid culture techniques, genetically engineered mouse models of injury and cancer, and human cell lines and specimens, lung progenitor cell studies can begin with basic biology, progress to translational research and finally lead to the beginnings of clinical trials.

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Essential Role for Activated Leukocyte Cell Adhesion Molecule Gene Silencing by GATA-1 in Megakaryocytic Progenitor Cell Biology.

Blood ◽

10.1182/blood.v108.11.1194.1194 ◽

2006 ◽

Vol 108 (11) ◽

pp. 1194-1194

Author(s):

Fang Tan ◽

Robert Thomas ◽

Flaubert Mbeunkui ◽

Solomon F. Ofori-Acquah

Keyword(s):

Cell Adhesion ◽

Cell Lines ◽

Adhesion Molecule ◽

Cell Biology ◽

Progenitor Cell ◽

Cell Adhesion Molecule ◽

K562 Cells ◽

Jurkat Cells ◽

Erythroid Progenitor ◽

Erythroid Progenitor Cell

Abstract Regulation of hematopoietic progenitor cell lineage-commitment, proliferation and differentiation by cell-cell adhesion mechanisms is poorly understood. Activated leukocyte cell adhesion molecule (ALCAM) is a member of the immunoglobulin super family. It is expressed by human hematopoietic stem cells, bone marrow stromal cells, endothelial cells and osteoblasts. Monoclonal anti-ALCAM antibodies inhibit myeloid but not erythroid colony formation, which suggest a lineage-specific role for ALCAM in hematopoiesis. To explore this hypothesis, ALCAM mRNA and protein expression was quantified in human hematopoietic cell lines of myeloid, lymphoid, erythroid, and megakaryocytic lineages by real-time quantitative PCR and western blot analyses. No ALCAM transcripts were detected in K562 and MEG-01 cells, the level of ALCAM mRNA was 2-fold more abundant in HL-60 and THP-1 cells than in U937 and Jurkat cells. This expression pattern was confirmed at the protein level as none of the megakaryocyte-erythroid progenitor cell lines (K562, MEG-01 and HEL) expressed ALCAM. On the contrary, ALCAM was abundantly expressed in THP-1 and HL-60 cells and moderately in U937 and Jurkat cells. GATA-1 was abundantly expressed in megakaryocyte-erythroid progenitor cell lines but not in any of the myeloid cell lines. Thus, there is an inverse relationship between expression of ALCAM and GATA-1 in hematopoietic cells. To test the hypothesis that GATA-1 is involved in silencing ALCAM gene expression, multiple ALCAM-promoter luciferase constructs were studied. A negative regulatory region was identified in the ALCAM promoter containing an inverted GATA-1 cis element at −850 upstream of the translational start site. GATA-1 occupied this canonical element in vivo as determined by chromatin immunoprecipitation experiments. A two-base pair mutation of the −850 GATA-1 cis element increased ALCAM promoter activity 3-fold in K562 and MEG-01 cells, providing direct evidence of GATA-1’s negative regulatory role in ALCAM promoter activity. To test the hypothesis that ALCAM silencing is essential for megakaryocyte-erythroid progenitor cell biology, stable lines of K562 cells were established forcibly expressing ALCAM-GFP or a control GFP. Live cell imaging demonstrated recruitment of ALCAM to sites of cell-cell adhesion in ALCAM-GFP-K562 cells, whereas GFP remained distributed in the cell cytosol in control cells. ALCAM-GFP-K562 cells formed markedly more clusters consisting of significantly more cells than control GFP-K562 cells. Finally, the number of ALCAM-GFP-K562 cells at log-phase growth was significantly higher than GFP-K562 cells over the same time period. Our findings demonstrate for the first time lineage-specific silencing of the cell adhesion molecule ALCAM in megakaryocyte-erythroid progenitor cells, mediated at least in part by GATA-1. That ectopic expression of ALCAM increased proliferation of K562 cells suggests that GATA-1-mediated silencing of ALCAM is essential in slowing down expansion of megakaryocyte-erythroid progenitor cells. Indeed, preliminary studies show an excessive number of erythroid and megakaryocytic cells in the adult spleen of ALCAM-null mice. This model is being used in ongoing studies to confirm our findings in vivo.

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Hematopoietic Stem and Progenitor Cell Biology in the Zebrafish.

Blood ◽

10.1182/blood.v108.11.4160.4160 ◽

2006 ◽

Vol 108 (11) ◽

pp. 4160-4160

Author(s):

David Traver ◽

Julien Bertrand ◽

Albert Kim ◽

Jennifer Cisson ◽

Emily Violette

Keyword(s):

Cell Biology ◽

Progenitor Cell ◽

Zebrafish Embryo ◽

Functional Characterization ◽

Hematopoietic Stem ◽

Blood Island ◽

The Past ◽

Transgenic Lines ◽

Zebrafish Embryogenesis

Abstract Over the past decade, the development of forward genetic approaches in the zebrafish system has provided unprecedented power in understanding the molecular basis of vertebrate blood development. Establishment of cellular and hematological approaches to better understand the biology of resulting blood mutants, however, has lagged behind these efforts. We have recently developed the means to identify zebrafish hematopoietic stem cells (HSCs), transgenic lines to mark hematopoietic precursors and their progeny, and the assays to test these populations functionally. Like other vertebrates, zebrafish demonstrate differential waves of hematopoiesis during embryogenesis. These waves can be visualized directly by fluorescent transgenesis in living embryos. The earliest blood-forming cells in the zebrafish embryo express the scl and lmo2 genes. By directing expression of GFP to early blood precursors using the lmo2 promoter, we have isolated early hematopoietic cells by flow cytometry and tested them functionally by transplantation. Transplantation of lmo2::GFP+ cells isolated from embryos at 14 hours post-fertilization (hpf) resulted in only transient reconstitution of erythrocytes, suggesting that the earliest identifiable blood-forming cells are committed to the erythroid lineage. Later in embryogenesis, lmo2:GFP+ GATA-1:dsRED+ cells are found in the posterior blood island (PBI) from approximately 30–60 hpf. Molecular and functional characterization of these cells suggests that they possess limited myeloid and erythroid, but not lymphoid differentiation potentials. This suggests that committed progenitors with definitive hematopoietic potential arise in the embryo before HSCs can be identified. Additional studies have suggested that the first multipotent HSCs are born later in the zebrafish aorta/gonad/mesonephros (AGM) region. We have visualized putative HSCs in the AGM by their expression of the lmo2 and cd41 transgenes. Using confocal timelapse imaging in living embryos, lmo2::GFP+ cells have been observed to emigrate from the AGM region into circulation. Transplantation studies are underway to test putative HSC populations for repopulation activity. Taken together, our findings suggest that at least three independent waves of blood cell precursors are formed during zebrafish embryogenesis.

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Advantages of anchoring growth factors to materials for neural stem/progenitor cell proliferation

Journal of Materials Chemistry B ◽

10.1039/c6tb01944g ◽

2016 ◽

Vol 4 (37) ◽

pp. 6213-6220 ◽

Cited By ~ 2

Author(s):

T. Nakaji-Hirabayashi ◽

K. Fujimoto ◽

Y. Kato ◽

H. Kitano ◽

Y. Inoue ◽

...

Keyword(s):

Cell Proliferation ◽

Growth Factors ◽

Growth Factor ◽

Cell Biology ◽

Progenitor Cell ◽

Materials Science ◽

Progenitor Cell Proliferation

We tried to clarify the mechanisms underlying immobilized-growth factor in NSPC regulation using approaches from materials science and cell biology.

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Effects of androgens on endothelial progenitor cells in vitro and in vivo

Clinical Science ◽

10.1042/cs20090077 ◽

2009 ◽

Vol 117 (10) ◽

pp. 355-364 ◽

Cited By ~ 22

Author(s):

Gian Paolo Fadini ◽

Mattia Albiero ◽

Andrea Cignarella ◽

Chiara Bolego ◽

Christian Pinna ◽

...

Keyword(s):

Progenitor Cells ◽

Endothelial Progenitor Cells ◽

Endothelial Progenitor Cell ◽

Cell Biology ◽

Progenitor Cell ◽

Adult Males ◽

Endothelial Progenitor ◽

Healthy Human

The beneficial or detrimental effects of androgens on the cardiovascular system are debated. Endothelial progenitor cells are bone-marrow-derived cells involved in endothelial healing and angiogenesis, which promote cardiovascular health. Oestrogens are potent stimulators of endothelial progenitor cells, and previous findings have indicated that androgens may improve the biology of these cells as well. In the present study, we show that testosterone and its active metabolite dihydrotestosterone exert no effects on the expansion and function of late endothelial progenitors isolated from the peripheral blood of healthy human adult males, whereas they positively modulate early ‘monocytic’ endothelial progenitor cells. In parallel, we show that castration in rats is followed by a decrease in circulating endothelial progenitor cells, but that testosterone and dihydrotestosterone replacement fails to restore endothelial progenitor cells towards normal levels. This is associated with persistently low oestrogen levels after androgen replacement in castrated rats. In a sample of 62 healthy middle-aged men, we show that circulating endothelial progenitor cell levels are more directly associated with oestradiol, rather than with testosterone, concentrations. In conclusion, our results collectively demonstrate that androgens exert no direct effects on endothelial progenitor cell biology in vitro and in vivo.

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Integrated Genomic Analysis of Diverse Induced Pluripotent Stem Cells from the Progenitor Cell Biology Consortium

Stem Cell Reports ◽

10.1016/j.stemcr.2016.05.006 ◽

2016 ◽

Vol 7 (1) ◽

pp. 110-125 ◽

Cited By ~ 51

Author(s):

Nathan Salomonis ◽

Phillip J. Dexheimer ◽

Larsson Omberg ◽

Robin Schroll ◽

Stacy Bush ◽

...

Keyword(s):

Stem Cells ◽

Induced Pluripotent Stem Cells ◽

Pluripotent Stem Cells ◽

Cell Biology ◽

Progenitor Cell ◽

Genomic Analysis ◽

Induced Pluripotent

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Depression and Antidepressants During Pregnancy: Craniofacial Defects Due to Stem/Progenitor Cell Deregulation Mediated by Serotonin

Frontiers in Cell and Developmental Biology ◽

10.3389/fcell.2021.632766 ◽

2021 ◽

Vol 9 ◽

Author(s):

Natalia Sánchez ◽

Jesús Juárez-Balarezo ◽

Marcia Olhaberry ◽

Humberto González-Oneto ◽

Antonia Muzard ◽

...

Keyword(s):

Pregnant Women ◽

Maternal Depression ◽

Progenitor Cells ◽

Cell Biology ◽

Progenitor Cell ◽

Selective Serotonin Reuptake Inhibitors ◽

Craniofacial Development ◽

Serotonin Signaling ◽

Associated Risk Factors ◽

Craniofacial Defects

Depression is a common and debilitating mood disorder that increases in prevalence during pregnancy. Worldwide, 7 to 12% of pregnant women experience depression, in which the associated risk factors include socio-demographic, psychological, and socioeconomic variables. Maternal depression could have psychological, anatomical, and physiological consequences in the newborn. Depression has been related to a downregulation in serotonin levels in the brain. Accordingly, the most commonly prescribed pharmacotherapy is based on selective serotonin reuptake inhibitors (SSRIs), which increase local serotonin concentration. Even though the use of SSRIs has few adverse effects compared with other antidepressants, altering serotonin levels has been associated with the advent of anatomical and physiological changes in utero, leading to defects in craniofacial development, including craniosynostosis, cleft palate, and dental defects. Migration and proliferation of neural crest cells, which contribute to the formation of bone, cartilage, palate, teeth, and salivary glands in the craniofacial region, are regulated by serotonin. Specifically, craniofacial progenitor cells are affected by serotonin levels, producing a misbalance between their proliferation and differentiation. Thus, it is possible to hypothesize that craniofacial development will be affected by the changes in serotonin levels, happening during maternal depression or after the use of SSRIs, which cross the placental barrier, increasing the risk of craniofacial defects. In this review, we provide a synthesis of the current research on depression and the use of SSRI during pregnancy, and how this could be related to craniofacial defects using an interdisciplinary perspective integrating psychological, clinical, and developmental biology perspectives. We discuss the mechanisms by which serotonin could influence craniofacial development and stem/progenitor cells, proposing some transcription factors as mediators of serotonin signaling, and craniofacial stem/progenitor cell biology. We finally highlight the importance of non-pharmacological therapies for depression on fertile and pregnant women, and provide an individual analysis of the risk–benefit balance for the use of antidepressants during pregnancy

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