scholarly journals In vivo clonal analysis reveals spatiotemporal regulation of thalamic nucleogenesis

2017 ◽  
Author(s):  
Samuel Z.H. Wong ◽  
Earl Parker Scott ◽  
Wenhui Mu ◽  
Xize Guo ◽  
Ella Borgenheimer ◽  
...  
Keyword(s):  
Progenitor Cells ◽  
Clonal Analysis ◽  
Cellular Heterogeneity ◽  
Thalamic Nuclei ◽  
Fate Specification ◽  
Cell Divisions ◽  
Spatiotemporal Regulation ◽  
Short Period ◽  
Organizational Principle

ABSTRACTThe thalamus, a crucial regulator of cortical functions, is composed of many nuclei arranged in a spatially complex pattern. Thalamic neurogenesis occurs over a short period during mammalian embryonic development. These features have hampered the effort to understand how regionalization, cell divisions and fate specification are coordinated and produce a wide array of nuclei that exhibit distinct patterns of gene expression and functions. Here, we performed in vivo clonal analysis to track the divisions of individual progenitor cells and spatial allocation of their progeny in the developing mouse thalamus. Quantitative analysis of clone compositions revealed evidence for sequential generation of distinct sets of thalamic nuclei based on the location of the founder progenitor cells. Furthermore, we identified intermediate progenitor cells that produced neurons populating more than one thalamic nuclei, indicating a prolonged specification of nuclear fate. Our study reveals an organizational principle that governs the spatial and temporal progression of cell divisions and fate specification, and provides a framework for studying cellular heterogeneity and connectivity in the mammalian thalamus.

scholarly journals CD70/CD27 signaling promotes blast stemness and is a viable therapeutic target in acute myeloid leukemia

2016 ◽  
Vol 214 (2) ◽  
pp. 359-380 ◽  
Author(s):  
Carsten Riether ◽  
Christian M. Schürch ◽  
Elias D. Bührer ◽  
Magdalena Hinterbrandner ◽  
Anne-Laure Huguenin ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Stem Cell ◽  
Progenitor Cells ◽  
Myeloid Leukemia ◽  
Hematopoietic Stem ◽  
Cell Divisions ◽  
Cell Gene ◽  
Stem Cell Gene ◽  
Acute Myeloid

Aberrant proliferation, symmetric self-renewal, increased survival, and defective differentiation of malignant blasts are key oncogenic drivers in acute myeloid leukemia (AML). Stem cell gene signatures predict poor prognosis in AML patients; however, with few exceptions, these deregulated molecular pathways cannot be targeted therapeutically. In this study, we demonstrate that the TNF superfamily ligand–receptor pair CD70/CD27 is expressed on AML blasts and AML stem/progenitor cells. CD70/CD27 signaling in AML cells activates stem cell gene expression programs, including the Wnt pathway, and promotes symmetric cell divisions and proliferation. Soluble CD27, reflecting the extent of CD70/CD27 interactions in vivo, was significantly elevated in the sera of newly diagnosed AML patients and is a strong independent negative prognostic biomarker for overall survival. Blocking the CD70/CD27 interaction by mAb induced asymmetric cell divisions and differentiation in AML blasts and AML stem/progenitor cells, inhibited cell growth and colony formation, and significantly prolonged survival in murine AML xenografts. Importantly, hematopoietic stem/progenitor cells from healthy BM donors express neither CD70 nor CD27 and were unaffected by blocking mAb treatment. Therefore, targeting CD70/CD27 signaling represents a promising therapeutic strategy for AML.

scholarly journals Single cell dynamics of embryonic muscle progenitor cells in zebrafish

2018 ◽  
Author(s):  
Priyanka Sharma ◽  
Tyler D. Ruel ◽  
Katrinka M. Kocha ◽  
Shan Liao ◽  
Peng Huang
Keyword(s):  
Single Cell ◽  
Progenitor Cells ◽  
Muscle Injury ◽  
Muscle Growth ◽  
Clonal Analysis ◽  
Muscle Stem Cells ◽  
Injury Repair ◽  
Embryonic Muscle ◽  
Muscle Progenitor Cells

ABSTRACTMuscle stem cells hold a great therapeutic potential in regenerating damaged muscles. However, the in vivo behavior of muscle stem cells during muscle growth and regeneration is still poorly understood. Using zebrafish as a model, we describe the in vivo dynamics and function of dermomyotome cells, a population of embryonic muscle progenitor cells. Dermomyotome cells are located in a superficial layer external to muscle fibers and express many extracellular matrix (ECM) genes including col1a2. Utilizing a new col1a2 transgenic line, we show that dermomyotome cells display a ramified morphology with dynamic cellular processes. Cell lineage tracing demonstrates that col1a2+ dermomyotome cells contribute to normal muscle growth as well as muscle injury repair. Combination of live imaging and single cell clonal analysis reveals a highly-choreographed process of muscle regeneration. Activated dermomyotome cells change from the quiescent ramified morphology to a polarized and elongated morphology and generate daughter cells that fuse with existing muscle fibers. Ablation of the dermomyotome severely compromises muscle injury repair. Our work provides a dynamic view of embryonic muscle progenitor cells during zebrafish muscle regeneration.Summary statementLive imaging and single cell clonal analysis reveal dynamic behaviors of zebrafish embryonic muscle progenitor cells in quiescence and activation.

scholarly journals In vivo clonal analysis reveals spatiotemporal regulation of thalamic nucleogenesis

PLoS Biology ◽  
2018 ◽  
Vol 16 (4) ◽  
pp. e2005211 ◽  
Author(s):  
Samuel Z. H. Wong ◽  
Earl Parker Scott ◽  
Wenhui Mu ◽  
Xize Guo ◽  
Ella Borgenheimer ◽  
...  
Keyword(s):  
Clonal Analysis ◽  
Spatiotemporal Regulation

scholarly journals Visualization of individual cell division history in complex tissues

2020 ◽  
Author(s):  
Annina Denoth-Lippuner ◽  
Baptiste N. Jaeger ◽  
Tong Liang ◽  
Stefanie E. Chie ◽  
Lars N. Royall ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cell Division ◽  
Progenitor Cells ◽  
Individual Cell ◽  
Cell Divisions ◽  
Mouse Tissues ◽  
Single Cell Rna Sequencing ◽  
Neural Stem Progenitor Cells

SummaryThe division potential of individual stem cells and the molecular consequences of successive rounds of proliferation remain largely unknown. We developed an inducible cell division counter (iCOUNT) that reports cell division events in human and mouse tissues in vitro and in vivo. Analysing cell division histories of neural stem/progenitor cells (NSPCs) in the developing and adult brain, we show that iCOUNT allows for novel insights into stem cell behaviour. Further, we used single cell RNA-sequencing (scRNA-seq) of iCOUNT-labelled NSPCs and their progenies from the developing mouse cortex and forebrain-regionalized human organoids to identify molecular pathways that are commonly regulated between mouse and human cells, depending on individual cell division histories. Thus, we developed a novel tool to characterize the molecular consequences of repeated cell divisions of stem cells that allows an analysis of the cellular principles underlying tissue formation, homeostasis, and repair.HighlightsiCOUNT reports previous cell divisions in mouse and human cells in vitroiCOUNT detects cell division biographies in complex mouse tissues in vivoiCOUNT allows for the analysis of human neural stem/progenitor cells in human forebrain organoidsSingle cell RNA-sequencing of iCOUNT cells derived from the mouse developing cortex and human forebrain organoids identifies molecular consequences of previous rounds of cell divisionsGraphical abstract

Significance of In-Vitro and In-Vivo Correlation in Drug Delivery System

2018 ◽  
Vol 4 (4) ◽  
pp. 523-531
Author(s):  
Hina Mumtaz ◽  
Muhammad Asim Farooq ◽  
Zainab Batool ◽  
Anam Ahsan ◽  
Ashikujaman Syed
Keyword(s):  
Dosage Form ◽  
Pharmaceutical Preparations ◽  
Pharmacokinetic Profile ◽  
In Vitro Dissolution ◽  
Time Saving ◽  
Pharmaceutical Dosage Form ◽  
Short Period ◽  
Form Development

The main purpose of development pharmaceutical dosage form is to find out the in vivo and in vitro behavior of dosage form. This challenge is overcome by implementation of in-vivo and in-vitro correlation. Application of this technique is economical and time saving in dosage form development. It shortens the period of development dosage form as well as improves product quality. IVIVC reduce the experimental study on human because IVIVC involves the in vivo relevant media utilization in vitro specifications. The key goal of IVIVC is to serve as alternate for in vivo bioavailability studies and serve as justification for bio waivers. IVIVC follows the specifications and relevant quality control parameters that lead to improvement in pharmaceutical dosage form development in short period of time. Recently in-vivo in-vitro correlation (IVIVC) has found application to predict the pharmacokinetic behaviour of pharmaceutical preparations. It has emerged as a reliable tool to find the mode of absorption of several dosage forms. It is used to correlate the in-vitro dissolution with in vivo pharmacokinetic profile. IVIVC made use to predict the bioavailability of the drug of particular dosage form. IVIVC is satisfactory for the therapeutic release profile specifications of the formulation. IVIVC model has capability to predict plasma drug concentration from in vitro dissolution media.

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.

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.

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