Id4 regulates neural progenitor proliferation and differentiation in vivo

Development ◽  
2004 ◽  
Vol 131 (21) ◽  
pp. 5441-5448 ◽  
Author(s):  
K. Yun
Keyword(s):  
Neural Progenitor ◽  
Proliferation And Differentiation

scholarly journals Myelin basic protein enhances axonal regeneration from neural progenitor cells

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Zhengjian Yan ◽  
Lei Chu ◽  
Xiaojiong Jia ◽  
Lu Lin ◽  
Si Cheng
Keyword(s):  
Myelin Basic Protein ◽  
Neurite Outgrowth ◽  
Progenitor Cells ◽  
Axonal Regeneration ◽  
Neural Progenitor Cells ◽  
Basic Protein ◽  
Neural Progenitor ◽  
Dependent Manner ◽  
Cord Injury

Abstract Introduction Stem cell therapy using neural progenitor cells (NPCs) shows promise in mitigating the debilitating effects of spinal cord injury (SCI). Notably, myelin stimulates axonal regeneration from mammalian NPCs. This led us to hypothesize that myelin-associated proteins may contribute to axonal regeneration from NPCs. Methods We conducted an R-based bioinformatics analysis to identify key gene(s) that may participate in myelin-associated axonal regeneration from murine NPCs, which identified the serine protease myelin basic protein (Mbp). We employed E12 murine NPCs, E14 rat NPCs, and human iPSC-derived Day 1 NPCs (D1 hNPCs) with or without CRISPR/Cas9-mediated Mbp knockout in combination with rescue L1-70 overexpression, constitutively-active VP16-PPARγ2, or the PPARγ agonist ciglitazone. A murine dorsal column crush model of SCI utilizing porous collagen-based scaffolding (PCS)-seeded murine NPCs with or without stable Mbp overexpression was used to assess locomotive recovery and axonal regeneration in vivo. Results Myelin promotes axonal outgrowth from NPCs in an Mbp-dependent manner and that Mbp’s stimulatory effects on NPC neurite outgrowth are mediated by Mbp’s production of L1-70. Furthermore, we determined that Mbp/L1-70’s stimulatory effects on NPC neurite outgrowth are mediated by PPARγ-based repression of neuron differentiation-associated gene expression and PPARγ-based Erk1/2 activation. In vivo, PCS-seeded murine NPCs stably overexpressing Mbp significantly enhanced locomotive recovery and axonal regeneration in post-SCI mice. Conclusions We discovered that Mbp supports axonal regeneration from mammalian NPCs through the novel Mbp/L1cam/Pparγ signaling pathway. This study suggests that bioengineered, NPC-based interventions can promote axonal regeneration and functional recovery post-SCI.

scholarly journals The Great Capacity on Promoting Melanogenesis of Three Compatible Components in Vernonia anthelmintica (L.) Willd.

2021 ◽  
Vol 22 (8) ◽  
pp. 4073
Author(s):  
Yifan Lai ◽  
Qingyuan Feng ◽  
Rui Zhang ◽  
Jing Shang ◽  
Hui Zhong
Keyword(s):  
Herbal Medicine ◽  
Caffeic Acid ◽  
Fluorescent Protein ◽  
Traditional Chinese Herbal Medicine ◽  
Expression Of Genes ◽  
Proliferation And Differentiation ◽  
Green Fluorescent ◽  
Vernonia Anthelmintica

To investigate a possible methodology of exploiting herbal medicine and design polytherapy for the treatment of skin depigmentation disorder, we have made use of Vernonia anthelmintica (L.) Willd., a traditional Chinese herbal medicine that has been proven to be effective in treating vitiligo. Here, we report that the extract of Vernonia anthelmintica (L.) Willd. effectively enhances melanogenesis responses in B16F10. In its compound library, we found three ingredients (butin, caffeic acid and luteolin) also have the activity of promoting melanogenesis in vivo and in vitro. They can reduce the accumulation of ROS induced by hydrogen peroxide and inflammatory response induced by sublethal concentrations of copper sulfate in wild type and green fluorescent protein (GFP)-labeled leukocytes zebrafish larvae. The overall objective of the present study aims to identify which compatibility proportions of the medicines may be more effective in promoting pigmentation. We utilized the D-optimal response surface methodology to optimize the ratio among three molecules. Combining three indicators of promoting melanogenesis, anti-inflammatory and antioxidant capacities, we get the best effect of butin, caffeic acid and luteolin at the ratio (butin:caffeic acid:luteolin = 7.38:28.30:64.32) on zebrafish. Moreover, the effect of melanin content recovery in the best combination is stronger than that of the monomer, which suggests that the three compounds have a synergistic effect on inducing melanogenesis. After simply verifying the result, we performed in situ hybridization on whole-mount zebrafish embryos to further explore the effects of multi-drugs combination on the proliferation and differentiation of melanocytes and the expression of genes (tyr, mitfa, dct, kit) related to melanin synthesis. In conclusion, the above three compatible compounds can significantly enhance melanogenesis and improve depigmentation in vivo.

MO243STUDY ON THE EFFECT AND MECHANISM OF NOVEL REGULATORY T CELL (CD4+CD126LOWFOXP3+ TREG) IMMUNOTHERAPY IN LUPUS NEPHRITIS*

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Zhenjian Xu ◽  
Junzhe Chen ◽  
Anping Xu
Keyword(s):  
T Cell ◽  
Lupus Nephritis ◽  
Signaling Pathway ◽  
B Lymphocytes ◽  
Mtor Signaling ◽  
Mtor Signaling Pathway ◽  
Proliferation And Differentiation ◽  
Inflammatory State

Abstract Background and Aims Our previous study found a new regulatory T cell subpopulation, CD4+CD126lowFoxp3+ regulatory T cells (CD4+CD126lowFoxp3+ Treg). This cell can maintain a stable immune regulatory function in the inflammatory state. Through in vivo and in vitro experiments, we have confirmed that CD4+CD126lowFoxp3+ Treg has an immunotherapeutic effect on T cell-mediated mouse models of autoimmune diseases such as colitis and collagen-induced arthritis (CIA). Further experimental studies showed that CD4+CD126lowFoxp3+ Treg could reduce the kidney injury caused by autoantibodies and prolong the survival time of lupus mice. However, the mechanism of CD4+CD126lowFoxp3+ Treg immunotherapy in lupus nephritis is not clear. The purpose of this study was to explore the mechanism of CD4+CD126lowFoxp3+ Treg immunotherapy in mice with lupus nephritis. Method In vitro experiments CD4+CD126lowFoxp3+ Treg or CD4+CD126lowFoxp3+ Treg pretreated with PD-1 inhibitor were co-cultured with T or B lymphocytes of lupus mice under different in vitro culture condition. The expression levels of Akt and mTOR of Treg in each group were measured under immunoinflammatory conditions. To observe the effects and differences of Treg groups on the activation, proliferation and differentiation of T or B cells and other immunomodulatory effects. In vivo experiments CD4+CD126lowFoxp3+ Treg (2 × 106/mouse) and CD4+CD126lowFoxp3+ Treg (2 × 106/mouse) pretreated with PD-1 inhibitor and PBS were injected into NZM2328 lupus mice, respectively. After cell injection, urine protein was measured weekly. Autoantibody expression in lupus mice was measured every two weeks. The effects of Treg on the proliferation and differentiation of T/B cells in lupus mice were observed. The therapeutic effects of Treg on lupus mice were observed. Results Compared with CD4+CD126lowFoxp3+ Treg, the expression of Akt and mTOR increases in PD-1 inhibitors pretreatment cells. The activation, proliferation and differentiation functions of T or B lymphocytes of lupus mice were significantly weakened by immunosuppression of PD-1 inhibitors pretreated Treg in vitro, indicating that CD4+CD126lowFoxp3+ Treg may inhibit Akt-mTOR signaling pathway through PD-1 in in vitro. Compared with CD4+CD126lowFoxp3+ Treg, the activation, proliferation and differentiation functions of T or B lymphocytes of lupus mice were significantly weakened by immunosuppression of PD-1 inhibitors pretreated Treg in vivo. And its therapeutic effect on lupus mice was ineffective, indicating that CD4+CD126lowFoxp3+ Treg may inhibit Akt-MTOR signaling pathway through PD-1 in vivo. Conclusion CD4+CD126lowFoxp3+ Treg may inhibit the Akt-mTOR signaling pathway by expressing PD-1, and maintain stable immunomodulatory function in the inflammatory state, thus producing immunotherapeutic effect on lupus nephritis mice.

scholarly journals Effects of Naringin on Proliferation and Osteogenic Differentiation of Human Periodontal Ligament Stem Cells In Vitro and In Vivo

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Lihua Yin ◽  
Wenxiao Cheng ◽  
Zishun Qin ◽  
Hongdou Yu ◽  
Zhanhai Yu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Osteogenic Differentiation ◽  
Periodontal Ligament ◽  
Trabecular Structure ◽  
Control Group ◽  
Periodontal Ligament Stem Cells ◽  
Expression Levels ◽  
Proliferation And Differentiation

This study is to explore the osteogenesis potential of the human periodontal ligament stem cells (hPDLSCs) induced by naringin in vitro and in vitro. The results confirmed that 1 μM naringin performs the best effect and a collection of bone-related genes (RUNX2,COL1A2, OPN, and OCN) had significantly higher expression levels compared to the control group. Furthermore, a typical trabecular structure was observed in vivo, surrounded by a large amount of osteoblasts. These results demonstrated that naringin, at a concentration of 1 μM, can efficiently promote the proliferation and differentiation of hPDLSCs both in vitro and in vivo.

scholarly journals Isolation and characterization of adrenocortical progenitors involved in the adaptation to stress

2018 ◽  
Vol 115 (51) ◽  
pp. 12997-13002 ◽  
Author(s):  
Charlotte Steenblock ◽  
Maria F. Rubin de Celis ◽  
Luis F. Delgadillo Silva ◽  
Verena Pawolski ◽  
Ana Brennand ◽  
...  
Keyword(s):  
Lineage Tracing ◽  
Differentiated Cells ◽  
Isolation And Characterization ◽  
Proliferation And Differentiation ◽  
Response To Stress ◽  
Steroidogenic Cells ◽  
High Degree

The adrenal gland is a master regulator of the human body during response to stress. This organ shows constant replacement of senescent cells by newly differentiated cells. A high degree of plasticity is critical to sustain homeostasis under different physiological demands. This is achieved in part through proliferation and differentiation of adult adrenal progenitors. Here, we report the isolation and characterization of a Nestin+ population of adrenocortical progenitors located under the adrenal capsule and scattered throughout the cortex. These cells are interconnected with progenitors in the medulla. In vivo lineage tracing revealed that, under basal conditions, this population is noncommitted and slowly migrates centripetally. Under stress, this migration is greatly enhanced, and the cells differentiate into steroidogenic cells. Nestin+ cells cultured in vitro also show multipotency, as they differentiate into mineralocorticoid and glucocorticoid-producing cells, which can be further influenced by the exposure to Angiotensin II, adrenocorticotropic hormone, and the agonist of luteinizing hormone-releasing hormone, triptorelin. Taken together, Nestin+ cells in the adult adrenal cortex exhibit the features of adrenocortical progenitor cells. Our study provides evidence for a role of Nestin+ cells in organ homeostasis and emphasizes their role under stress. This cell population might be a potential source of cell replacement for the treatment of adrenal insufficiency.

scholarly journals Mechanics of the cellular microenvironment as perceived by cells in vivo

2021 ◽  
Author(s):  
Alessandro Mongera ◽  
Marie Pochitaloff ◽  
Hannah J. Gustafson ◽  
Georgina A. Stooke-Vaughan ◽  
Payam Rowghanian ◽  
...  
Keyword(s):  
Stress Relaxation ◽  
Mechanical Parameters ◽  
Cellular Microenvironment ◽  
Stem Cell Maintenance ◽  
Quantitative Studies ◽  
Cell Proliferation And Differentiation ◽  
3D Microenvironment ◽  
Proliferation And Differentiation

Tissue morphogenesis and repair, as well as organ homeostasis, require cells to constantly monitor their 3D microenvironment and adapt their behaviors in response to local biochemical and mechanical cues1-6. In vitro studies have shown that substrate stiffness and stress relaxation are important mechanical parameters in the control of cell proliferation and differentiation, stem cell maintenance, cell migration 7-11, as well as tumor progression and metastasis12,13. Yet, the mechanical parameters of the microenvironment that cells perceive in vivo, within 3D tissues, remain unknown. In complex materials with strain- and time-dependent material properties, the perceived mechanical parameters depend both on the strain and timescales at which the material is mechanically probed14. Here, we quantify in vivo and in situ the mechanics of the cellular microenvironment that cells probe during vertebrate presomitic mesoderm (PSM) specification. By analyzing the magnitude and dynamics of endogenous, cell-generated strains, we show that individual cells preferentially probe the stiffness associated with deformations of the supracellular, foam-like tissue architecture. We reveal how stress relaxation leads to a perceived microenvironment stiffness that decreases over time, with cells probing the softest regime. While stress relaxation timescales are spatially uniform in the tissue, most mechanical parameters, including those probed by cells, vary along the anteroposterior axis, as mesodermal progenitors commit to different lineages. Understanding the mechanical parameters that cells probe in their native 3D environment is important for quantitative studies of mechanosensation in vivo2-4,6,15 and can help design scaffolds for tissue engineering applications16-18.

TWEAK regulates proliferation and differentiation of adult neural progenitor cells

2011 ◽  
Vol 46 (1) ◽  
pp. 325-332 ◽  
Author(s):  
Marion N. Schölzke ◽  
Amely Röttinger ◽  
Sasidhar Murikinati ◽  
Nadine Gehrig ◽  
Christoph Leib ◽  
...  
Keyword(s):  
Progenitor Cells ◽  
Neural Progenitor Cells ◽  
Neural Progenitor ◽  
Proliferation And Differentiation

scholarly journals Developmental aspects of adipose tissue in GH receptor and prolactin receptor gene disrupted mice: site-specific effects upon proliferation, differentiation and hormone sensitivity

2006 ◽  
Vol 191 (1) ◽  
pp. 101-111 ◽  
Author(s):  
David J Flint ◽  
Nadine Binart ◽  
Stephanie Boumard ◽  
John J Kopchick ◽  
Paul Kelly
Keyword(s):  
Adipose Tissue ◽  
Receptor Gene ◽  
Metabolic Effects ◽  
Wild Type ◽  
Extrinsic Factors ◽  
Differentiation Potential ◽  
Site Specific ◽  
Proliferation And Differentiation

Direct metabolic effects of GH on adipose tissue are well established, but effects of prolactin (PRL) have been more controversial. Recent studies have demonstrated PRL receptors on adipocytes and effects of PRL on adipose tissue in vitro. The role of GH in adipocyte proliferation and differentiation is also controversial, since GH stimulates adipocyte differentiation in cell lines, whereas it stimulates proliferation but inhibits differentiation of adipocytes in primary cell culture. Using female gene disrupted (ko) mice, we showed that absence of PRL receptors (PRLRko) impaired development of both internal and s.c. adipose tissue, due to reduced numbers of adipocytes, an effect differing from that of reduced food intake, where cell volume is decreased. In contrast, GHRko mice exhibited major decreases in the number of internal adipocytes, whereas s.c. adipocyte numbers were increased, even though body weight was decreased by 40–50%. The changes in adipose tissue in PRLRko mice appeared to be entirely due to extrinsic factors since preadipocytes proliferated and differentiated in similar fashion to wild-type animals in vitro and their response to insulin and isoproterenol was similar to wild-type animals. This contrasted with GHRko mice, where s.c. adipocytes proliferated, differentiated, and responded to hormones in identical fashion to controls, whereas parametrial adipocytes exhibited markedly depressed proliferation and differentiation potential and failed to respond to insulin or noradrenaline. Our results provide in vivo evidence that both GH and PRL stimulate differentiation of adipocytes but that the effects of GH are site specific and induce intrinsic changes in the precursor population, which are retained in vitro.

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