scholarly journals Control of neurogenic competence in mammalian hypothalamic tanycytes

2021 ◽  
Vol 7 (22) ◽  
pp. eabg3777
Author(s):  
Sooyeon Yoo ◽  
Juhyun Kim ◽  
Pin Lyu ◽  
Thanh V. Hoang ◽  
Alex Ma ◽  
...  
Keyword(s):  
Single Cell ◽  
Molecular Mechanisms ◽  
Radial Glial Cells ◽  
Neuronal Progenitors ◽  
Physiological Processes ◽  
Internal States ◽  
Nuclear Factor I ◽  
Radial Glial ◽  
Accessible Chromatin ◽  
Deficient Mice

Hypothalamic tanycytes, radial glial cells that share many features with neuronal progenitors, can generate small numbers of neurons in the postnatal hypothalamus, but the identity of these neurons and the molecular mechanisms that control tanycyte-derived neurogenesis are unknown. In this study, we show that tanycyte-specific disruption of the NFI family of transcription factors (Nfia/b/x) robustly stimulates tanycyte proliferation and tanycyte-derived neurogenesis. Single-cell RNA sequencing (scRNA-seq) and single-cell assay for transposase-accessible chromatin sequencing (scATAC-seq) analysis reveals that NFI (nuclear factor I) factors repress Sonic hedgehog (Shh) and Wnt signaling in tanycytes and modulation of these pathways blocks proliferation and tanycyte-derived neurogenesis in Nfia/b/x-deficient mice. Nfia/b/x-deficient tanycytes give rise to multiple mediobasal hypothalamic neuronal subtypes that can mature, fire action potentials, receive synaptic inputs, and selectively respond to changes in internal states. These findings identify molecular mechanisms that control tanycyte-derived neurogenesis, which can potentially be targeted to selectively remodel the hypothalamic neural circuitry that controls homeostatic physiological processes.

scholarly journals Control of neurogenic competence in mammalian hypothalamic tanycytes

2020 ◽  
Author(s):  
Sooyeon Yoo ◽  
Juhyun Kim ◽  
Pin Lyu ◽  
Thanh V. Hoang ◽  
Alex Ma ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Molecular Mechanisms ◽  
Neural Circuitry ◽  
Radial Glial Cells ◽  
Neuronal Progenitors ◽  
Physiological Processes ◽  
Internal States ◽  
Radial Glial ◽  
Synaptic Circuitry ◽  
Deficient Mice

AbstractHypothalamic tanycytes, radial glial cells that share many features with neuronal progenitors, generate small numbers of neurons in the postnatal hypothalamus, but the identity of these neurons and the molecular mechanisms that control tanycyte-derived neurogenesis are unknown. In this study, we demonstrate that tanycyte-specific disruption of the NFI family of transcription factors (Nfia/b/x) robustly stimulates tanycyte proliferation and tanycyte-derived neurogenesis. Single-cell RNA- and ATAC-Seq analysis reveals that NFI factors repress Shh and Wnt signaling in tanycytes, and small molecule modulation of these pathways blocks proliferation and tanycyte-derived neurogenesis in Nfia/b/x-deficient mice. We show that Nfia/b/x-deficient tanycytes give rise to multiple mediobasal hypothalamic neuronal subtypes that can mature, integrate into hypothalamic synaptic circuitry, and selectively respond to changes in internal states. These findings identify molecular mechanisms that control tanycyte-derived neurogenesis, suggesting a new therapeutic approach to selectively remodel the hypothalamic neural circuitry that controls homeostatic physiological processes.

scholarly journals Function of Macrophages in Disease: Current Understanding on Molecular Mechanisms

2021 ◽  
Vol 12 ◽  
Author(s):  
Chunye Zhang ◽  
Ming Yang ◽  
Aaron C. Ericsson
Keyword(s):  
Single Cell ◽  
Molecular Mechanisms ◽  
Lymphoid Tissues ◽  
Metabolic Function ◽  
Tissue Microenvironment ◽  
Physiological Processes ◽  
Cellular Debris ◽  
Single Cell Rna Sequencing ◽  
Macrophage Subpopulations ◽  
Diagnostic Approaches

Tissue-resident macrophages (TRMs) are heterogeneous populations originating either from monocytes or embryonic progenitors, and distribute in lymphoid and non-lymphoid tissues. TRMs play diverse roles in many physiological processes, including metabolic function, clearance of cellular debris, and tissue remodeling and defense. Macrophages can be polarized to different functional phenotypes depending on their origin and tissue microenvironment. Specific macrophage subpopulations are associated with disease progression. In studies of fate-mapping and single-cell RNA sequencing methodologies, several critical molecules have been identified to induce the change of macrophage function. These molecules are potential markers for diagnosis and selective targets for novel macrophage-mediated treatment. In this review, we discuss some of the recent findings regarding less-known molecules and new functions of well-known molecules. Understanding the mechanisms of these molecules in macrophages has the potential to yield new macrophage-mediated treatments or diagnostic approaches to disease.

scholarly journals Dentate gyrus development requires a cortical hem-derived astrocytic scaffold

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Alessia Caramello ◽  
Christophe Galichet ◽  
Karine Rizzoti ◽  
Robin Lovell-Badge
Keyword(s):  
Transcription Factors ◽  
Dentate Gyrus ◽  
Local Network ◽  
Radial Glial Cells ◽  
Neuronal Progenitor ◽  
Neuronal Progenitors ◽  
Radial Glial ◽  
Cortical Hem ◽  
Mouse Brain Development

During embryonic development, radial glial cells give rise to neurons, then to astrocytes following the gliogenic switch. Timely regulation of the switch, operated by several transcription factors, is fundamental for allowing coordinated interactions between neurons and glia. We deleted the gene for one such factor, SOX9, early during mouse brain development and observed a significantly compromised dentate gyrus (DG). We dissected the origin of the defect, targeting embryonic Sox9 deletion to either the DG neuronal progenitor domain or the adjacent cortical hem (CH). We identified in the latter previously uncharacterized ALDH1L1+ astrocytic progenitors, which form a fimbrial-specific glial scaffold necessary for neuronal progenitor migration towards the developing DG. Our results highlight an early crucial role of SOX9 for DG development through regulation of astroglial potential acquisition in the CH. Moreover, we illustrate how formation of a local network, amidst astrocytic and neuronal progenitors originating from adjacent domains, underlays brain morphogenesis.

scholarly journals ANO1/TMEM16A regulates process maturation in radial glial cells in the developing brain

2019 ◽  
Vol 116 (25) ◽  
pp. 12494-12499 ◽  
Author(s):  
Gyu-Sang Hong ◽  
Sung Hoon Lee ◽  
Byeongjun Lee ◽  
Jae Hyouk Choi ◽  
Soo-Jin Oh ◽  
...  
Keyword(s):  
Glial Cells ◽  
Ventricular Zone ◽  
Trophic Factors ◽  
Early Developmental Stage ◽  
Anoctamin 1 ◽  
Radial Glial Cells ◽  
Radial Glial ◽  
Early Developmental ◽  
The Brain ◽  
Deficient Mice

Neural stem cells (NSCs) are primary progenitor cells in the early developmental stage in the brain that initiate a diverse lineage of differentiated neurons and glia. Radial glial cells (RGCs), a type of neural stem cell in the ventricular zone, are essential for nurturing and delivering new immature neurons to the appropriate cortical target layers. Here we report that Anoctamin 1 (ANO1)/TMEM16A, a Ca2+-activated chloride channel, mediates the Ca2+-dependent process extension of RGCs. ANO1 is highly expressed and functionally active in RGCs of the mouse embryonic ventricular zone. Knockdown of ANO1 suppresses RGC process extension and protrusions, whereas ANO1 overexpression stimulates process extension. Among various trophic factors, brain-derived neurotrophic factor (BDNF) activates ANO1, which is required for BDNF-induced process extension in RGCs. More importantly, Ano1-deficient mice exhibited disrupted cortical layers and reduced cortical thickness. We thus conclude that the regulation of RGC process extension by ANO1 contributes to the normal formation of mouse embryonic brain.

scholarly journals Decoding Cortical Glial Cell Development

2021 ◽  
Author(s):  
Xiaosu Li ◽  
Guoping Liu ◽  
Lin Yang ◽  
Zhenmeiyu Li ◽  
Zhuangzhi Zhang ◽  
...  
Keyword(s):  
Single Cell ◽  
Glial Cell ◽  
Glial Cells ◽  
Cell Lineage ◽  
Gabaergic Interneurons ◽  
Rna Seq ◽  
Radial Glial Cells ◽  
Intermediate Progenitors ◽  
Late Embryogenesis ◽  
Radial Glial

AbstractMouse cortical radial glial cells (RGCs) are primary neural stem cells that give rise to cortical oligodendrocytes, astrocytes, and olfactory bulb (OB) GABAergic interneurons in late embryogenesis. There are fundamental gaps in understanding how these diverse cell subtypes are generated. Here, by combining single-cell RNA-Seq with intersectional lineage analyses, we show that beginning at around E16.5, neocortical RGCs start to generate ASCL1+EGFR+ apical multipotent intermediate progenitors (MIPCs), which then differentiate into basal MIPCs that express ASCL1, EGFR, OLIG2, and MKI67. These basal MIPCs undergo several rounds of divisions to generate most of the cortical oligodendrocytes and astrocytes and a subpopulation of OB interneurons. Finally, single-cell ATAC-Seq supported our model for the genetic logic underlying the specification and differentiation of cortical glial cells and OB interneurons. Taken together, this work reveals the process of cortical radial glial cell lineage progression and the developmental origins of cortical astrocytes and oligodendrocytes.

scholarly journals Dentate gyrus development requires a cortical hem-derived astrocytic scaffold

2020 ◽  
Author(s):  
Alessia Caramello ◽  
Christophe Galichet ◽  
Karine Rizzoti ◽  
Robin Lovell-Badge
Keyword(s):  
Transcription Factors ◽  
Dentate Gyrus ◽  
Local Network ◽  
Radial Glial Cells ◽  
Neuronal Progenitor ◽  
Neuronal Progenitors ◽  
Radial Glial ◽  
Cortical Hem ◽  
Mouse Brain Development

ABSTRACTDuring embryonic development, radial glial cells give rise to neurons, then to astrocytes following the gliogenic switch. Timely regulation of the switch, operated by several transcription factors, is fundamental for allowing coordinated interactions between neurons and glia. We deleted the gene for one such factor, SOX9, early during mouse brain development and observed a significantly compromised dentate gyrus (DG). We dissected the origin of the defect, targeting embryonic Sox9 deletion to either the DG neuronal progenitor domain or the adjacent cortical hem (CH). We identified in the latter previously uncharacterized ALDH1L1+ astrocytic progenitors, which form a fimbrial-specific glial scaffold necessary for neuronal progenitor migration towards the developing DG. Our results highlight an early crucial role of SOX9 for DG development through regulation of astroglial potential acquisition in the CH. Moreover, we illustrate how formation of a local network, amidst astrocytic and neuronal progenitors originating from adjacent domains, underlays brain morphogenesis.

scholarly journals Modeling progression of single cell populations through the cell cycle as a sequence of switches

2021 ◽  
Author(s):  
Andrei Zinovyev ◽  
Michail Sadovsky ◽  
Laurence Calzone ◽  
Aziz Fouché ◽  
Clarice S Groeneveld ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Single Cell ◽  
Molecular Mechanisms ◽  
System Size ◽  
Mechanistic Modeling ◽  
Cell Populations ◽  
Dynamical Process ◽  
Modeling Framework ◽  
Internal States ◽  
Fundamental Biological Process

Cell cycle is the most fundamental biological process underlying the existence and propagation of life in time and space. It has been an object for mathematical modeling for long, with several alternative mechanistic modeling principles suggested, describing in more or less details the known molecular mechanisms. Recently, cell cycle has been investigated at single cell level in snapshots of unsynchronized cell populations, exploiting the new methods for transcriptomic and proteomic molecular profiling. This raises a need for simplified semi-phenomenological cell cycle models, in order to formalize the processes underlying the cell cycle, at a higher abstracted level. Here we suggest a modeling framework, recapitulating the most important properties of the cell cycle as a limit trajectory of a dynamical process characterized by several internal states with switches between them. In the simplest form, this leads to a limit cycle trajectory, composed by linear segments in logarithmic coordinates describing some extensive (depending on system size) cell properties. We prove a theorem connecting the effective embedding dimensionality of the cell cycle trajectory with the number of its linear segments. We show how the developed formalism can be applied to model the available single cell datasets and simulate certain properties of the cell cycle trajectories.

scholarly journals Molecular Responses during Plant Grafting and Its Regulation by Auxins, Cytokinins, and Gibberellins

Biomolecules ◽  
2019 ◽  
Vol 9 (9) ◽  
pp. 397 ◽  
Author(s):  
Anket Sharma ◽  
Bingsong Zheng
Keyword(s):  
Plant Hormones ◽  
Growth And Development ◽  
Molecular Mechanisms ◽  
Main Process ◽  
Graft Union ◽  
Physiological Processes ◽  
Current Review ◽  
Postharvest Life ◽  
Successful Production

Plant grafting is an important horticulture technique used to produce a new plant after joining rootstock and scion. This is one of the most used techniques by horticulturists to enhance the quality and production of various crops. Grafting helps in improving the health of plants, their yield, and the quality of plant products, along with the enhancement of their postharvest life. The main process responsible for successful production of grafted plants is the connection of vascular tissues. This step determines the success rate of grafts and hence needs to be studied in detail. There are many factors that regulate the connection of scion and stock, and plant hormones are of special interest for researchers in the recent times. These phytohormones act as signaling molecules and have the capability of translocation across the graft union. Plant hormones, mainly auxins, cytokinins, and gibberellins, play a major role in the regulation of various key physiological processes occurring at the grafting site. In the current review, we discuss the molecular mechanisms of graft development and the phytohormone-mediated regulation of the growth and development of graft union.

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