Update on the Notochord Including its Embryology, Molecular Development, and Pathology: A Primer for the Clinician

Ramesh, Tushar; Nagula, Sai V; Tardieu, Gabrielle G; Saker, Erfanul; Shoja, Mohammadali Mohajel; Loukas, Marios; Oskouian, Rod J.; Tubbs, R. Shane

doi:10.7759/cureus.1137

Cited by 19 publications

(16 citation statements)

References 31 publications

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“…Cell-based regenerative therapy constitutes a highly promising and attractive strategy for restoration of NP cellularity and reconstitution of the healthy disc structure (Chan & Gantenbein-Ritter, 2012;Leung, Chan, & Cheung, 2006;Sakai, 2008). The NP of adult human is derived from a rod-like midline structure of mesodermal origin known as notochord (Ramesh et al, 2017). Since adult NP do not possess self regeneration capabilities, the NP cell renewal depends upon availability of progenitor cells which commit to the NP lineage and undergo terminal differentiation and produce an appropriate proteoglycan-rich matrix which is essential for the functioning of IVD (Stemple, 2005;Velikonja et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

Derivation of notochordal cells from human embryonic stem cells reveals unique regulatory networks by single cell‐transcriptomics

Díaz-Hernández

Khan

Trochez

et al. 2019

Journal Cellular Physiology

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Intervertebral disc degeneration (IDD) is a public health dilemma as it is associated with low back and neck pain, a frequent reason for patients to visit the physician. During IDD, nucleus pulposus (NP), the central compartment of intervertebral disc (IVD) undergo degeneration. Stem cells have been adopted as a promising biological source to regenerate the IVD and restore its function. Here, we describe a simple, two‐step differentiation strategy using a cocktail of four factors (LDN, AGN, FGF, and CHIR) for efficient derivation of notochordal cells from human embryonic stem cells (hESCs). We employed a CRISPR/Cas9 based genome‐editing approach to knock‐in the mCherry reporter vector upstream of the 3′ untranslated region of the Noto gene in H9‐hESCs and monitored notochordal cell differentiation. Our data show that treatment of H9‐hESCs with the above‐mentioned four factors for 6 days successfully resulted in notochordal cells. These cells were characterized by morphology, immunostaining, and gene and protein expression analyses for established notochordal cell markers including FoxA2, SHH, and Brachyury. Additionally, pan‐genomic high‐throughput single cell RNA‐sequencing revealed an efficient and robust notochordal differentiation. We further identified a key regulatory network consisting of eight candidate genes encoding transcription factors including PAX6, GDF3, FOXD3, TDGF1, and SOX5, which are considered as potential drivers of notochordal differentiation. This is the first single cell transcriptomic analysis of notochordal cells derived from hESCs. The ability to efficiently obtain notochordal cells from pluripotent stem cells provides an additional tool to develop new cell‐based therapies for the treatment of IDD.

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Section: Introductionmentioning

confidence: 99%

Derivation of notochordal cells from human embryonic stem cells reveals unique regulatory networks by single cell‐transcriptomics

Díaz-Hernández

Khan

Trochez

et al. 2019

Journal Cellular Physiology

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“…This structure is essential for the neural and endodermal patterning of e.g., the intestine, liver, and lungs. In vertebrates signaling molecules such as hedgehog proteins secreted by the notochord play key roles regarding differentiation and growth of the surrounding tissues ( 21 , 22 ).…”

Section: Recapitulation Of Human Organogenesismentioning

confidence: 99%

Embryology of the Abdominal Wall and Associated Malformations—A Review

et al. 2022

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In humans, the incidence of congenital defects of the intraembryonic celom and its associated structures has increased over recent decades. Surgical treatment of abdominal and diaphragmatic malformations resulting in congenital hernia requires deep knowledge of ventral body closure and the separation of the primary body cavities during embryogenesis. The correct development of both structures requires the coordinated and fine-tuned synergy of different anlagen, including a set of molecules governing those processes. They have mainly been investigated in a range of vertebrate species (e.g., mouse, birds, and fish), but studies of embryogenesis in humans are rather rare because samples are seldom available. Therefore, we have to deal with a large body of conflicting data concerning the formation of the abdominal wall and the etiology of diaphragmatic defects. This review summarizes the current state of knowledge and focuses on the histological and molecular events leading to the establishment of the abdominal and thoracic cavities in several vertebrate species. In chronological order, we start with the onset of gastrulation, continue with the establishment of the three-dimensional body shape, and end with the partition of body cavities. We also discuss well-known human etiologies.

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“…As stated earlier, chordoma are assumed to arise from remnants of the foetal notochord. The notochord is a rod-shaped embryologic structure that develops in the third week of gestation, and serves as an molecular inducer for vertebral column formation [ 69 ]. As the vertebral column develops, the notochord degrades into clusters in what later becomes the nucleus pulposus [ 70 ].…”

Section: Differential Diagnosismentioning

confidence: 99%

State-of-the-Art Imaging in Human Chordoma of the Skull Base

Santegoeds

Temel

Beckervordersandforth

et al. 2018

Curr Radiol Rep

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Purpose of ReviewChordoma are rare tumours of the axial skeleton which occur most often at the base of the skull and in the sacrum. Although chordoma are generally slow-growing lesions, the recurrence rate is high and the location makes it often difficult to treat. Both computed tomography (CT) and magnetic resonance imaging (MRI) are crucial in the initial diagnosis, treatment planning and post-treatment follow-up.Recent FindingsBasic MRI and CT characteristics of chordoma were described in the late 1980s and early 1990s. Since then, imaging techniques have evolved with increased resolution and new molecular imaging tools are rapidly evolving. New imaging tools have been developed not only to study anatomy, but also physiologic changes and characterization of tissue and assessment of tumour biology. Recent studies show the uptake of multiple PET tracers in chordoma, which may become an important aspect in the diagnosis, follow-up and personalized therapy.SummaryThis review gives an overview of skull base chordoma histopathology, classic imaging characteristics, radiomics and state-of-the-art imaging techniques that are now emerging in diagnosis, treatment planning and disease monitoring of skull base chordoma.

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Update on the Notochord Including its Embryology, Molecular Development, and Pathology: A Primer for the Clinician

Cited by 19 publications

References 31 publications

Derivation of notochordal cells from human embryonic stem cells reveals unique regulatory networks by single cell‐transcriptomics

Derivation of notochordal cells from human embryonic stem cells reveals unique regulatory networks by single cell‐transcriptomics

Embryology of the Abdominal Wall and Associated Malformations—A Review

State-of-the-Art Imaging in Human Chordoma of the Skull Base

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