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Fate map

Tanzila Mukhtar, Verdon Taylor
The cerebral cortex is composed of billions of morphologically and functionally distinct neurons. These neurons are produced and organized in a regimental fashion during development. The ability of neurons to encode and elicit complex cognitive and motor functions depends on their precise molecular processes, identity, and connectivity established during development. Elucidating the cellular and molecular mechanisms that regulate development of the neocortex has been a challenge for many years. The cerebral cortical neuronal subtypes are classified based on morphology, function, intrinsic synaptic properties, location, connectivity, and marker gene expression...
2018: Journal of Experimental Neuroscience
Battuya Bayarmagnai, Louisiane Perrin, Kamyar Esmaeili Pourfarhangi, Bojana Gligorijevic
Cancer cell motility and invasion are key features of metastatic tumors. Both are highly linked to tumor microenvironmental parameters, such as collagen architecture or macrophage density. However, due to the genetic, epigenetic and microenvironmental heterogeneities, only a small portion of tumor cells in the primary tumor are motile and furthermore, only a small portion of those will metastasize. This creates a challenge in predicting metastatic fate of single cells based on the phenotype they exhibit in the primary tumor...
2018: Methods in Molecular Biology
Charlene Babra Waryah, Colette Moses, Mahira Arooj, Pilar Blancafort
The completion of genome, epigenome, and transcriptome mapping in multiple cell types has created a demand for precision biomolecular tools that allow researchers to functionally manipulate DNA, reconfigure chromatin structure, and ultimately reshape gene expression patterns. Epigenetic editing tools provide the ability to interrogate the relationship between epigenetic modifications and gene expression. Importantly, this information can be exploited to reprogram cell fate for both basic research and therapeutic applications...
2018: Methods in Molecular Biology
Vanessa Donega, Guillaume Marcy, Quentin Lo Giudice, Stefan Zweifel, Diane Angonin, Roberto Fiorelli, Djoher Nora Abrous, Sylvie Rival-Gervier, Muriel Koehl, Denis Jabaudon, Olivier Raineteau
Progenitors of cortical glutamatergic neurons (Glu progenitors) are usually thought to switch fate before birth to produce astrocytes. We used fate-mapping approaches to show that a large fraction of Glu progenitors persist in the postnatal forebrain after closure of the cortical neurogenesis period. Postnatal Glu progenitors do not accumulate during embryonal development but are produced by embryonal radial glial cells that persist after birth in the dorsal subventricular zone and continue to give rise to cortical neurons, although with low efficiency...
March 6, 2018: Cell Reports
Timothy Sadlon, Cheryl Y Brown, Veronika Bandara, Christopher M Hope, John E Schjenken, Stephen M Pederson, James Breen, Alistair Forrest, Marc Beyer, Sarah Robertson, Simon C Barry
Regulatory T cells (Treg) are critical for preventing autoimmunity and curtailing responses of conventional effector T cells (Tconv). The reprogramming of T-cell fate and function to generate Treg requires switching on and off of key gene regulatory networks, which may be initiated by a subtle shift in expression levels of specific genes. This can be achieved by intermediary regulatory processes that include microRNA and long noncoding RNA-based regulation of gene expression. There are well-documented microRNA profiles in Treg and Tconv, and these can operate to either reinforce or reduce expression of a specific set of target genes, including FOXP3 itself...
2018: Clinical & Translational Immunology
Hui Zhang, Kathy O Lui, Bin Zhou
Endocardial cells are specialized endothelial cells that form the innermost layer of the heart wall. By virtue of genetic lineage-tracing technology, many of the unexpected roles of endocardium during murine heart development, diseases, and regeneration have been identified recently. In addition to heart valves developed from the well-known endothelial to mesenchymal transition, recent fate-mapping studies using mouse models reveal that multiple cardiac cell lineages are also originated from the endocardium...
March 2, 2018: Circulation Research
Guido Gambara, Manuela Gaebler, Ulrich Keilholz, Christian R A Regenbrecht, Alessandra Silvestri
Recent advances in next-generation sequencing and other omics technologies capable to map cell fate provide increasing evidence on the crucial role of intra-tumor heterogeneity (ITH) for cancer progression. The different facets of ITH, from genomic to microenvironmental heterogeneity and the hierarchical cellular architecture originating from the cancer stem cell compartment, contribute to the range of tumor phenotypes. Decoding these complex data resulting from the analysis of tumor tissue complexity poses a challenge for developing novel therapeutic strategies that can counteract tumor evolution and cellular plasticity...
2018: Frontiers in Pharmacology
Lijun Ren, Ding Tang, Tingting Zhao, Fanfan Zhang, Changzhen Liu, Zhihui Xue, Wenqing Shi, Guijie Du, Yi Shen, Yafei Li, Zhukuan Cheng
In angiosperms, the key step in sexual reproduction is successful acquisition of meiotic fate. However, the molecular mechanism determining meiotic fate remains largely unknown. Here, we report that OsSPOROCYTELESS (OsSPL) is critical for meiotic entry in rice (Oryza sativa). We performed a large-scale genetic screen of rice sterile mutants aimed to identify genes regulating meiotic entry and identified OsSPL using map-based cloning. We showed that meiosis-specific callose deposition, chromatin organization, and centromere-specific histone H3 loading were altered in the cells corresponding to pollen mother cells in Osspl anthers...
February 26, 2018: New Phytologist
Gregory F Pirrone, Rose M Mathew, Alexey A Makarov, Frank Bernardoni, Artis Klapars, Robert Hartman, John Limanto, Erik L Regalado
Impurity fate and purge studies are critical in order to establish an effective impurity control strategy for approval of the commercial filing application of new medicines. Reversed phase liquid chromatography-diode array-mass spectrometry (RPLC-DAD-MS) has traditionally been the preferred tool for impurity fate mapping. However, separation of some reaction mixtures by LC can be very problematic requiring combination LC-UV for area % analysis and a different LC-MS method for peak identification. In addition, some synthetic intermediates might be chemically susceptible to the aqueous conditions used in RPLC separations...
February 8, 2018: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
Yubin Huang, Zhen Xu, Shanshan Xiong, Fangfang Sun, Guangrong Qin, Guanglei Hu, Jingjing Wang, Lei Zhao, Yu-Xiang Liang, Tianzhun Wu, Zhonghua Lu, Mark S Humayun, Kwok-Fai So, Yihang Pan, Ningning Li, Ti-Fei Yuan, Yanxia Rao, Bo Peng
Newborn microglia rapidly replenish the whole brain after selective elimination of most microglia (>99%) in adult mice. Previous studies reported that repopulated microglia were largely derived from microglial progenitor cells expressing nestin in the brain. However, the origin of these repopulated microglia has been hotly debated. In this study, we investigated the origin of repopulated microglia by a series of fate-mapping approaches. We first excluded the blood origin of repopulated microglia via parabiosis...
February 22, 2018: Nature Neuroscience
Lay Teng Ang, Antson Kiat Yee Tan, Matias I Autio, Su Hua Goh, Siew Hua Choo, Kian Leong Lee, Jianmin Tan, Bangfen Pan, Jane Jia Hui Lee, Jen Jen Lum, Christina Ying Yan Lim, Isabelle Kai Xin Yeo, Chloe Jin Yee Wong, Min Liu, Jueween Ling Li Oh, Cheryl Pei Lynn Chia, Chet Hong Loh, Angela Chen, Qingfeng Chen, Irving L Weissman, Kyle M Loh, Bing Lim
How are closely related lineages, including liver, pancreas, and intestines, diversified from a common endodermal origin? Here, we apply principles learned from developmental biology to rapidly reconstitute liver progenitors from human pluripotent stem cells (hPSCs). Mapping the formation of multiple endodermal lineages revealed how alternate endodermal fates (e.g., pancreas and intestines) are restricted during liver commitment. Human liver fate was encoded by combinations of inductive and repressive extracellular signals at different doses...
February 20, 2018: Cell Reports
Dheva Setiaputra, Salar Ahmad, Udit Dalwadi, Anne-Lise Steunou, Shan Lu, James D Ross, Meng-Qiu Dong, Jacques Côté, Calvin K Yip
Conserved from yeast to humans, the NuA4 histone acetyltransferase is a large multisubunit complex essential for cell viability through regulation of gene expression, genome maintenance, metabolism, and cell fate during development and stress. How the different NuA4 subunits work in concert with one another to perform these diverse functions remains unclear, and addressing this central question requires a comprehensive understanding of NuA4's molecular architecture and subunit organization. We have determined the structure of fully assembled native yeast NuA4 by single-particle electron microscopy...
February 20, 2018: Molecular and Cellular Biology
Ramanpreet Kaur, Vikas
There are some unsettled issues regarding the mechanism and kinetics of an important atmospheric reaction of NO2 radical with the SH radical. The existing mechanism is based on the formation of HSO and NO radicals, both of which can result only along one barrierless channel. However, the detection of NO radical has never been reported though the formation of HSO radical has been followed in some studies to determine the rate constants. The latter are mainly obtained by monitoring the SH decay, but rate constants are reported to be highly conflicting among the existing studies reporting its value ranging from 10-10 to 10-12 cm3 molecule-1 sec-1 ...
February 19, 2018: Journal of Physical Chemistry. A
Veit R Buchholz, Michael Flossdorf
Single antigen-specific B or T lymphocytes are the smallest functional units, into which an adaptive immune response can be dissected. Today, novel high-throughput technologies are providing researches with increasingly complex information on the diverse phenotypic signatures of individual lymphocytes. With a focus on T cells, we summarize here, how computational approaches are becoming increasingly important to identify the relevant developmental boundaries and connections between these high-dimensional lymphocyte states...
2018: Advances in Immunology
Jia-Lin Mo, Qi Liu, Zeng-Wei Kou, Kun-Wei Wu, Ping Yang, Xian-Hua Chen, Feng-Yan Sun
Reactive astrocytes induced by ischemia can transdifferentiate into mature neurons. This neurogenic potential of astrocytes may have therapeutic value for brain injury. Epigenetic modifications are widely known to involve in developmental and adult neurogenesis. PAX6, a neurogenic fate determinant, contributes to the astrocyte-to-neuron conversion. However, it is unclear whether microRNAs (miRs) modulate PAX6-mediated astrocyte-to-neuron conversion. In the present study we used bioinformatic approaches to predict miRs potentially targeting Pax6, and transient middle cerebral artery occlusion (MCAO) to model cerebral ischemic injury in adult rats...
February 16, 2018: Glia
Nils O Lindström, Tracy Tran, Jinjin Guo, Elisabeth Rutledge, Riana K Parvez, Matthew E Thornton, Brendan Grubbs, Jill A McMahon, Andrew P McMahon
The nephron is the functional unit of the kidney, but the mechanism of nephron formation during human development is unclear. We conducted a detailed analysis of nephron development in humans and mice by immunolabeling, and we compared human and mouse nephron patterning to describe conserved and divergent features. We created protein localization maps that highlight the emerging patterns along the proximal-distal axis of the developing nephron and benchmark expectations for localization of functionally important transcription factors, which revealed unanticipated cellular diversity...
February 15, 2018: Journal of the American Society of Nephrology: JASN
Anya V Grozhik, Samie R Jaffrey
Messenger RNA (mRNA) and long noncoding RNA (lncRNA) can be subjected to a variety of post-transcriptional modifications that markedly influence their fate and function. This concept of 'epitranscriptomic' modifications and the understanding of their function has been driven by new technologies for transcriptome-wide mapping of modified nucleotides using next-generation sequencing. Mapping technologies have successfully documented the location and prevalence of several modified nucleotides in the transcriptome...
February 14, 2018: Nature Chemical Biology
Dunja Mrdjen, Anto Pavlovic, Felix J Hartmann, Bettina Schreiner, Sebastian G Utz, Brian P Leung, Iva Lelios, Frank L Heppner, Jonathan Kipnis, Doron Merkler, Melanie Greter, Burkhard Becher
Individual reports suggest that the central nervous system (CNS) contains multiple immune cell types with diverse roles in tissue homeostasis, immune defense, and neurological diseases. It has been challenging to map leukocytes across the entire brain, and in particular in pathology, where phenotypic changes and influx of blood-derived cells prevent a clear distinction between reactive leukocyte populations. Here, we applied high-dimensional single-cell mass and fluorescence cytometry, in parallel with genetic fate mapping systems, to identify, locate, and characterize multiple distinct immune populations within the mammalian CNS...
February 6, 2018: Immunity
Teresa Guillamon-Vivancos, William A Tyler, Maria Medalla, Wayne Wei-En Chang, Mayumi Okamoto, Tarik F Haydar, Jennifer I Luebke
How the variety of neurons that organize into neocortical layers and functional areas arises is a central question in the study of cortical development. While both intrinsic and extrinsic cues are known to influence this process, whether distinct neuronal progenitor groups contribute to neuron diversity and allocation is poorly understood. Using in vivo genetic fate-mapping combined with whole-cell patch clamp recording, we show that the firing pattern and apical dendritic morphology of excitatory neurons in layer 4 of the barrel cortex are specified in part by their neural precursor lineage...
February 3, 2018: Cerebral Cortex
Priyanka R Dharampuriya, Giorgia Scapin, Colline Wong, K John Wagner, Jennifer L Cillis, Dhvanit I Shah
PURPOSE OF REVIEW: The hierarchical nature of the hematopoietic system provides an ideal model system to illustrate the features of lineage tracing. We have outlined the utility of lineage tracing methods in establishing the origin and development of hematopoietic cells. RECENT FINDINGS: Methods such as CRISPR/Cas9, Polylox barcoding, and single-cell RNA-sequencing have improved our understanding of hematopoiesis. SUMMARY: This review chronicles the fate of the hematopoietic cells emerging from the mesoderm that subsequently develops into the adult blood lineages...
February 1, 2018: Current Opinion in Cell Biology
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