scholarly journals How Mesp1 makes a move

2016 ◽  
Vol 213 (4) ◽  
pp. 411-413 ◽  
Author(s):  
Robert G. Kelly
Keyword(s):  
Transcription Factors ◽  
Cell Migration ◽  
Progenitor Cells ◽  
Progenitor Cell ◽  
Fate Specification ◽  
Cell Biol ◽  
Multipotent Progenitor Cells

The transcription factors Mesp1 and Mesp2 have essential roles in the migration and specification of multipotent progenitor cells at the onset of cardiogenesis. Chiapparo et al. (2016. J. Cell Biol. http://dx.doi.org/10.1083/jcb.201505082) identify common Mesp functions in fate specification and Mesp1-specific targets controlling the speed and direction of progenitor cell migration.

Abstract 011: Transcriptional Basis Of Epicardial Progenitor Cell Activation During Heart Development, Regeneration And Repair

2013 ◽  
Vol 113 (suppl_1) ◽  
Author(s):  
Guo N Huang ◽  
Jeffrey E Thatcher ◽  
John McAnally ◽  
Yongli Kong ◽  
Xiaoxia Qi ◽  
...  
Keyword(s):  
Progenitor Cells ◽  
Heart Development ◽  
Progenitor Cell ◽  
Cell Activation ◽  
Cardiac Development ◽  
Expression System ◽  
Neutrophil Infiltration ◽  
Developmental Gene ◽  
Paracrine Factors ◽  
Multipotent Progenitor Cells

The epicardium encapsulates the heart and functions as a source of multipotent progenitor cells and paracrine factors essential for cardiac development and repair. Injury of the adult heart results in reactivation of epicardial progenitor cells, which reengages a developmental gene program, but the underlying transcriptional basis has not been delineated. We established a mouse embryonic heart organ culture and gene expression system that facilitated the identification of epicardial enhancers activated during heart development and injury. Epicardial activation of these enhancers depends on a combinatorial transcriptional code centered on C/EBP, HOX, MEIS, and GRAINYHEAD families of transcription factors. Furthermore, disruption of C/EBP signaling in the adult epicardium reduced injury-induced neutrophil infiltration and improved cardiac function. These findings reveal a transcriptional basis for epicardial progenitor cell activation during heart development and injury, providing a platform for enhancing cardioprotection and regeneration.

The GEF Lsc Regulates Hematopoietic Stem Cell Motility, Mobilization and Recruitment.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 1346-1346
Author(s):  
Isabelle Petit ◽  
Prashant Kaul ◽  
Daniel J. Lerner ◽  
Shahin Rafii
Keyword(s):  
Stem Cell ◽  
Cell Migration ◽  
Tumor Growth ◽  
Cell Motility ◽  
Progenitor Cells ◽  
Hematopoietic Stem Cell ◽  
Tumor Angiogenesis ◽  
Progenitor Cell ◽  
Hematopoietic Stem ◽  
Stem And Progenitor Cells

Abstract Lsc is a Rho GTPase guanine nucleotide exchange factor (RhoGEF) that physically and functionally links G-protein coupled receptors (GPCR) to the monomeric GTPase RhoA in mature hematopoietic and other cells. Lsc−/− (LscKO) mice have a peripheral leukocytosis, abnormal neutrophil and B cell motility, and immune response deficiencies. Although Lsc is required for neutrophil homeostasis, its role in hematopoietic stem and progenitor cells is unknown. In this study, we have used LscKO mice to determine if Lsc is required for normal stem cell motility and mobilization. Initially, we used immunofluorescence labeling to demonstrate that hematopoietic stem and progenitor cells express Lsc. This suggested that Lsc may be required for normal hematopoietic stem and progenitor cell migration. Stromal-cell derived factor-1 (SDF-1) is a potent chemokine for hematopoietic stem cells and activates the CXCR4 GPCR. It has been reported that Lsc is not required for SDF-1-stimulated migration of mature murine T and B cells. However, using a bare-filter transwell assay, we found that while LscKO Sca-1+ cells and Sca-1+Lin- cells have normal spontaneous migration, they have significantly increased SDF-1-stimulated migration compared to their wild-type (WT) counterparts, 1.4 and 2.3 fold, respectively. We then demonstrated that adhesion of LscKO Sca-1+ cells to bone marrow (BM) stromal MS-5 cells was normal, indicating that impaired adhesion was not responsible for the abnormal SDF-1-stimulated migration. Using colony assay, we demonstrated that LscKO mice have a normal number of circulating peripheral stem and progenitor cells. Strikingly, after 5 days of G-CSF administration, LscKO mice have 1.6 fold and 2.3 fold the number of peripheral mature WBC and stem and progenitor cells (colony forming units), respectively, compared to WT mice. Recruitment of BM CXCR4+ pro-angiogenic stem and progenitor cells has been linked to enhanced tumor angiogenesis. Because LscKO BM cells had abnormal SDF-1-stimulated migration and mobilization, we hypothesized that Lsc might regulate tumor angiogenesis as well. To this end, we assessed tumor growth in LscKO mice by injecting congenic Lewis lung carcinoma cells subcutaneously into LscKO mice and WT controls. Preliminary experiments revealed that tumors were 3.3 times larger in the LscKO mice as compared to WT mice. Quantification of the tumor vessels with anti-CD31 staining demonstrated that the tumors in LscKO mice were 1.4 fold more vascularized than controls. In summary, our results demonstrate that the Rho GEF Lsc is essential for normal hematopoietic stem cell migration and mobilization. In addition, we propose that absence of Lsc facilitates tumor growth by promoting BM stem and progenitor cell recruitment to the neo-angiogenic vessels, possibly augmenting tumor vascularization.

scholarly journals Increased avidity for Dpp/BMP2 maintains the proliferation of eye progenitors in Drosophila

2015 ◽  
Author(s):  
Marta Neto ◽  
Fernando Casares
Keyword(s):  
Transcription Factors ◽  
Progenitor Cells ◽  
Progenitor Cell ◽  
Normal Development ◽  
Local Environment ◽  
Proliferative Potential ◽  
Normal Organ ◽  
Extracellular Signals ◽  
Extracellular Matrix Components ◽  
Tsh Cells

During normal organ development, the progenitor cell state is transient: it depends on specific combinations of transcription factors and extracellular signals, that cooperate to sustain the proliferative potential and undifferentiated status of organ progenitor cells. Not surprisingly, abnormal maintenance of progenitor transcription factors may lead to tissue overgrowth, and the concurrence of specific signals from the local environment is often critical to trigger this overgrowth. Therefore, the identification of the specific combinations of transcription factors and signals that promote or oppose proliferation in progenitor cells is essential to understand normal development and disease. We have investigated this issue by asking what signals may promote the proliferation of eye progenitors in Drosophila. Two transcription factors, the MEIS1 homologue homothorax (hth) and the Zn-finger teashirt (tsh) are transiently expressed in eye progenitors causing the expansion of the progenitor pool. However, if their co-expression is maintained experimentally, cell proliferation continues and differentiation is halted. Here we show that Hth+Tsh-induced tissue overgrowth requires the BMP2 ligand Dpp and the activation of its pathway. In Hth+Tsh cells, the Dpp pathway is abnormally hyperactivated. Rather than using autocrine Dpp expression, Hth+Tsh cells increase their avidity for Dpp, produced locally, by upregulating extracellular matrix components. During normal development, Dpp represses hth and tsh ensuring that the progenitor state is transient. However, cells in which Hth+Tsh expression is maintained use Dpp to enhance their proliferation.

Progenitor Cell Differentiation Into Dendritic Cells Requires Cytokine Mediated PKC-IRF Relationships

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 2449-2449
Author(s):  
Haley Spangler ◽  
Matthew R Farren ◽  
Louise M Carlson ◽  
Scott Abrams ◽  
Kelvin P Lee
Keyword(s):  
Transcription Factors ◽  
Progenitor Cells ◽  
Nuclear Localization ◽  
Progenitor Cell ◽  
Vaccine Development ◽  
Conflicts Of Interest ◽  
Human Monocytes ◽  
Gm Csf ◽  
Image Stream ◽  
Pkc Activation

Abstract Dendritic Cell (DC) differentiation is a complex system involving multiple progenitors with potential to differentiate into a variety of DC subsets. Understanding the mechanisms regulating these differentiation pathways is critical to understanding how defective DCs arise in cancer. Impaired DC differentiation often results in immunosuppressive cells that either hinder immune activation in disease or promote tumor growth and metastasis. We previously established that the serine-threonine kinase Protein Kinase C β isoform II (PKCβII) is required for human DC differentiation from CD34+ progenitor cells and monocytes, and have recently found that murine bone marrow (BM) cells also need it to become fully differentiated and functional DCs. However, the molecular targets of PKCβII in this pathway remain unclear. It is well established that the transcription factors Interferon Regulatory Factors 4 and 8 (IRF4 and IRF8) are also important for DC differentiation. IRF4 is crucial for the development of conventional DCs (mediated by GM-CSF), while IRF8 is crucial for the development of plasmacytoid and CD8α+DCs (mediated by FLT3-L). We hypothesized that a relationship existed between PKCβII and IRF4/8, and investigated the effects of PKC activation on IRF4/8 expression. Using human progenitor cell lines and murine BM cells we found that PKC activation upregulated IRF4 and IRF8 expression, while PKC inhibition downregulated IRF4 and IRF8. PKC inhibition also prevented these cells from differentiating into DCs, as determined by their phenotypic markers, physical characteristics, and T-cell stimulatory activity. However, we found that in progenitor cells GM-CSF (a known PKCβII activator) decreased IRF8 expression while upregulating IRF4 expression. This led us to investigate the differential effects of GM-CSF and FLT3-L on the PKC-IRF relationship. We saw that FLT3-L treatment of murine BM cells caused an upregulation of IRF8 and stimulated DC differentiation, and that DC differentiation and IRF8 upregulation were both lost in the presence of a PKC inhibitor. Using Image Stream analysis we found that FLT3-L treatment of progenitor cells activated PKCβII and PKCα. To determine which PKC(s) mediates the FLT3-L driven upregulation of IRF8, we used PKCα knockout (KO) BM and saw that cells were still able to differentiate into DCs and IRF8 levels were still being upregulated. Thus, PKCβII is the PKC that mediates FLT3-L driven DC differentiation and IRF8 upregulation. To determine what molecules could be acting downstream of PKCβII in regulating IRF4/8, we again used Image Stream analysis and visualized STAT3 and STAT5 translocation into the nucleus. Using murine BM cells we found that STAT3 and IRF8 nuclear localization increased with FLT3-L treatment, while GM-CSF treatment caused increased STAT5 and IRF4 nuclear localization. When looking at human monocytes and the human monocytic progenitor cell lineTHP-1 we saw similar effects: GM-CSF treatment increased STAT5 and IRF4 nuclear localization, while pan-PKC inhibition decreased basal STAT5 and IRF4 nuclear localization. Interestingly, these human monocytes and THP-1 cells had lower nuclear levels of STAT3 and IRF8 following FLT3-L treatment – possibly because these cells are already somewhat committed to the monocyte-derived conventional DC pathway. However, in murine early progenitor cells, after 15 minutes of PKC activation we saw increased STAT3 activation, indicating that PKC-regulated STAT3 activation is playing a role earlier in the differentiation process. To find the progenitor cells immediately effected by PKCβII activation, we used IRF8-eGFP murine BM and saw that PKC activation caused induced IRF8 expression as early as in the multi-potent progenitor cells (MPP2 and MPP3), and this upregulation continued to increase as cells differentiated to CD11b+progenitor cells and GMP. These studies indicate that PKCβII is activated in progenitor cells by either FLT3-L or GM-CSF, causing an upregulation of IRF8 or IRF4, respectively. PKCβII may be acting through STAT5 and STAT3 to induce IRF4 and IRF8, depending on the cytokine treatment. By having a better understanding of how PKCβII regulates the expression of these transcription factors, which are required for DC differentiation, we can manipulate the PKCβII-IRF relationship to drive or impair DC differentiation in pathological settings, and may improve DC-vaccine development. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Chromatin alterations in the aging lung change progenitor cell activity

2021 ◽  
Author(s):  
Samuel P. Rowbotham ◽  
Patrizia Pessina ◽  
Carolina Garcia de Alba Rivas ◽  
Jingyun Li ◽  
Irene Wong ◽  
...  
Keyword(s):  
Progenitor Cells ◽  
Progenitor Cell ◽  
Cell Activity ◽  
Cell Types ◽  
Chromatin Accessibility ◽  
Alveolar Type ◽  
Aged Mouse ◽  
Efficient Manner ◽  
Age Related ◽  
Multipotent Progenitor Cells

The lung contains multiple progenitor cell types that respond to damage, but how their responses are choreographed and why they decline with age is poorly understood. We report that histone H3 lysine 9 di-methylation (K9me2), mediated by histone methyltransferase G9a, regulates the dynamics of lung epithelial progenitor cells, and this regulation deteriorates with age. In aged mouse lungs, K9me2 loss coincided with lower frequency and activity of alveolar type 2 (AT2) cell progenitors. In contrast, K9me2 loss resulted in increased frequency and activity of multipotent progenitor cells with bronchiolar and alveolar potential (BASCs) and bronchiolar progenitors. K9me2 depletion in young mice through deletion or inhibition of G9a decreased AT2 progenitor activity and impaired alveolar injury regeneration. Conversely, K9me2 depletion increased chromatin accessibility of bronchiolar cell genes, increased BASC frequency and accelerated bronchiolar repair. K9me2 depletion also resulted in increased bronchiolar cell expression of the SARS-CoV2 receptor Ace2 in aged lungs. These data point to K9me2 and G9a as a critical regulator of the balance of lung progenitor cell regenerative responses and prevention of susceptibility to age-related lung diseases. These findings indicate that epigenetic regulation coordinates progenitor cell populations to expedite regeneration in the most efficient manner and disruption of this regulation presents significant challenges to lung health.

Sequential specification of neurons and glia by developmentally regulated extracellular factors

Development ◽  
2001 ◽  
Vol 128 (18) ◽  
pp. 3585-3594 ◽  
Author(s):  
Theresa Morrow ◽  
Mi-Ryoung Song ◽  
Anirvan Ghosh
Keyword(s):  
Progenitor Cells ◽  
Cell Fate ◽  
Developmental Stages ◽  
Developmentally Regulated ◽  
Fate Specification ◽  
Multipotent Progenitor Cells ◽  
Glial Fate ◽  
Sequential Generation ◽  
Cortical Slices ◽  
Cortical Progenitor

Cortical progenitor cells give rise to neurons during embryonic development and to glia after birth. While lineage studies indicate that multipotent progenitor cells are capable of generating both neurons and glia, the role of extracellular signals in regulating the sequential differentiation of these cells is poorly understood. To investigate how factors in the developing cortex might influence cell fate, we developed a cortical slice overlay assay in which cortical progenitor cells are cultured over cortical slices from different developmental stages. We find that embryonic cortical progenitors cultured over embryonic cortical slices differentiate into neurons and those cultured over postnatal cortical slices differentiate into glia, suggesting that the fate of embryonic progenitors can be influenced by developmentally regulated signals. In contrast, postnatal progenitor cells differentiate into glial cells when cultured over either embryonic or postnatal cortical slices. Clonal analysis indicates that the postnatal cortex produces a diffusible factor that induces progenitor cells to adopt glial fates at the expense of neuronal fates. The effects of the postnatal cortical signals on glial cell differentiation are mimicked by FGF2 and CNTF, which induce glial fate specification and terminal glial differentiation respectively. These observations indicate that cell fate specification and terminal differentiation can be independently regulated and suggest that the sequential generation of neurons and glia in the cortex is regulated by a developmental increase in gliogenic signals.

Abstract 9: Smooth Muscle Cells Are Crucial for Vascular Stem Cell Migration and Vasculogenesis via Keratinocyte Cell-derived Chemokine

2015 ◽  
Vol 35 (suppl_1) ◽  
Author(s):  
Baoqi Yu ◽  
Mei M Wong ◽  
Claire Potter ◽  
Yanhua Hu ◽  
Wen Wang ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Cell Migration ◽  
Smooth Muscle Cells ◽  
Progenitor Cells ◽  
Progenitor Cell ◽  
Muscle Cells ◽  
P38 Map Kinase ◽  
Keratinocyte Cell

Introduction: Recently, a population of stem/progenitor cells have been identified within the adventitia of vessel walls. While existing data indicate their capacity of differentiation into specific vascular lineages, their migratory roles within vascular diseases remain unknown. Interestingly, smooth muscle cells (SMCs) have been shown to reside within close proximity with the progenitors within the medial layer and thus may have a putative role on the motility of progenitor cells. Hypothesis: We hypothesize that mouse adventitia-derived resident progenitor cells will migrate in response to SMCs via their secretion of specific chemokine(s). Methods and Results: In vitro transwell and wound healing migration assays showed significant increases in Sca-1 + vascular progenitor cell migration in response to both SMCs and SMC-conditioned medium (CM). A chemokine ELISA array revealed that keratinocyte cell-derived chemokine (KC) level was markedly increased in SMC-CM. Exogenous recombinant KC significantly increased progenitor cell migration and KC knockdown in SMC-CM using siRNA markedly inhibited progenitor migration. The expression of its receptor, CXCR2, was upregulated following treatment with SMC-CM and treatment with a CXCR2 antagonist was found to significantly inhibit SMC-mediated progenitor migration. Furthermore, we found that the p38 MAP kinase pathway was involved in SMC-mediated migration; the phosphorylation of p38 in response to SMC-CM was partially reduced following knockdown with KC SiRNA. The migration of progenitor cells was also significantly decreased following treatment with a p38 inhibitor. Using a matrigel plug angiogenesis assay in vivo , we found that the KC induced Sca-1 + progenitors migration and enhanced markedly vasculogenesis after 2 weeks. The functional knockdown of KC in C57BL/6 mice using a KC morpholino system potentially reduces Sca-1 + progenitor cell migration compared to corresponding controls (n≥4 per group). Conclusion: In conclusion, SMCs can induce Sca-1 + progenitor cell migration via the release of KC and subsequent activation of p38 MAPK signalling pathway via CXCR2. The lack of functional KC inhibited progenitor cell migration and vasculogenesis in vivo .

scholarly journals Pdx-1 and Ptf1a concurrently determine fate specification of pancreatic multipotent progenitor cells

2008 ◽  
Vol 316 (1) ◽  
pp. 74-86 ◽  
Author(s):  
Jared S. Burlison ◽  
Qiaoming Long ◽  
Yoshio Fujitani ◽  
Christopher V.E. Wright ◽  
Mark A. Magnuson
Keyword(s):  
Progenitor Cells ◽  
Fate Specification ◽  
Multipotent Progenitor Cells
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