Publications by authors named "Unnikrishnan Sivan"

Neural Stem Progenitor Cells (NSPCs) maintenance and neuronal cell differentiation are the two key aspects of sustained neurogenesis in the adult mammalian brain. Transcription factors (TFs) are known to regulate these biological processes under the influence of various neurotrophic factors. Understanding the role of key TF genes in regulating adult neurogenesis is essential for determining the functional complexity and neuronal diversity seen in the adult mammalian brain.

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Background: Isolation of adult Neural Stem/Progenitor Cells (NSPCs) from their neurogenic niches, is a prerequisite for studies involving culturing of NSPCs as neurospheres or attached monolayers in vitro. The currently available protocols involve the use of multiple animals and expensive reagents to establish the NSPCs culture.

New Method: This unit describes a method to isolate and culture NSPCs from the two neurogenic niches in the mouse brain, the Subventricular Zone (SVZ) and Dentate gyrus (DG)/subgranular zone (SGZ), in an easy and cost-effective manner.

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The touch dome (TD) keratinocytes are specialized epidermal cells that intimately associate with the light touch sensing Merkel cells (MCs). The TD keratinocytes function as a niche for the MCs and can induce de novo hair follicles upon stimulation; however, how the TD keratinocytes are maintained during homeostasis remains unclear. scRNA-seq identified a specific TD keratinocyte marker, (TNC).

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Parkinson's disease (PD) is a neurodegenerative disorder, prevalent in the elderly population. Neuropathological hallmarks of PD include loss of dopaminergic cells in the nigro-striatal pathway and deposition of alpha-synuclein protein in the neurons and synaptic terminals, which lead to a complex presentation of motor and non-motor symptoms. This review focuses on various aspects of PD, from clinical diagnosis to currently accepted treatment options, such as pharmacological management through dopamine replacement and surgical techniques such as deep brain stimulation (DBS).

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Blood vessels provide supportive microenvironments for maintaining tissue functions. Age-associated vascular changes and their relation to tissue aging and pathology are poorly understood. Here, we perform 3D imaging of young and aging vascular beds.

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Hair follicle (HF) development is orchestrated by coordinated signals from adjacent epithelial and mesenchymal cells. In humans this process only occurs during embryogenesis and viable strategies to induce new HFs in adult skin are lacking. Here, we reveal that activation of Hedgehog (Hh) signaling in adjacent epithelial and stromal cells induces new HFs in adult, unwounded dorsal mouse skin.

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Skin homeostasis is orchestrated by dozens of cell types that together direct stem cell renewal, lineage commitment, and differentiation. Here, we use single-cell RNA sequencing and single-molecule RNA FISH to provide a systematic molecular atlas of full-thickness skin, determining gene expression profiles and spatial locations that define 56 cell types and states during hair growth and rest. These findings reveal how the outer root sheath (ORS) and inner hair follicle layers coordinate hair production.

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Skeletal vasculature plays a central role in the maintenance of microenvironments for osteogenesis and haematopoiesis. In addition to supplying oxygen and nutrients, vasculature provides a number of inductive factors termed as angiocrine signals. Blood vessels drive recruitment of osteoblast precursors and bone formation during development.

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The dynamics and interactions between stem cell pools in the hair follicle (HF), sebaceous gland (SG), and interfollicular epidermis (IFE) of murine skin are still poorly understood. In this study, we used multicolor lineage tracing to mark Lgr6⁺ -expressing basal cells in the HF isthmus, SG, and IFE.We show that these Lgr6⁺ cells constitute long-term self-renewing populations within each compartment in adult skin.

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Epithelialization of chronic cutaneous wound is troublesome and may require use of skin/cell substitutes. Adipose-derived mesenchymal stem cells (ADMSCs) have immense potential as autologous cell source for treating wounds; they can cross the germ layer boundary of differentiation and regenerate skin. When multipotent adult stem cells are considered for skin regeneration, lineage committed keratinocytes may be beneficial to prevent undesirable post-transplantation outcome.

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Commercially available skin substitutes lack essential non-immune cells for adequate tissue regeneration of non-healing wounds. A tissue-engineered, patient-specific, dermal substitute could be an attractive option for regenerating chronic wounds, for which adipose-derived mesenchymal stem cells (ADMSCs) could become an autologous source. However, ADMSCs are multipotent in nature and may differentiate into adipocytes, osteocytes and chondrocytes in vitro, and may develop into undesirable tissues upon transplantation.

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