Enteric glial cell heterogeneity regulates intestinal stem cell niches

Baghdadi, Meryem B.; Ayyaz, Arshad; Coquenlorge, Sabrina; Chu, Bonnie; Kumar, Sandeep; Streutker, Catherine; Wrana, Jeffrey L.; Kim, Tae-Hee

doi:10.1016/j.stem.2021.10.004

Cited by 61 publications

(41 citation statements)

References 68 publications

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“…Generally, both types of organoids lack complex mesenchymal heterogeneity and architecture, vasculature, neuronal connections and interaction with immune cells and the intestinal microbial flora. Several groups have therefore explored possible co-culture strategies to increase organoid complexity, including co-culture with endothelial ( Palikuqi et al, 2020 ), mesenchymal ( Stzepourginski et al, 2017 ), immune ( Bar-Ephraim et al, 2020 ) and glial cells ( Baghdadi et al, 2022 ), as well as microbial ( Finkbeiner et al, 2012 ; Wilson et al, 2015 ; Fatehullah et al, 2016 ; Han et al, 2019 ; Barron et al, 2020 ) and viral interactions ( Zhao et al, 2021 ). Yet, current co-culture systems are still relatively simple, only combining one or few cell types simultaneously.…”

Section: Limitations Of Intestinal Organoidsmentioning

confidence: 99%

“…et al, 2020 ). Specific subpopulations of Gfap + enteric glial cells (EGCs), localised near crypts, also provide key yet redundant Wnt factors to ISCs ( Baghdadi et al, 2022 ). In case of injury however, these EGCs expand and are critical to efficient intestinal regeneration ( Baghdadi et al, 2022 ).…”

Section: Introductionmentioning

confidence: 99%

“…Specific subpopulations of Gfap + enteric glial cells (EGCs), localised near crypts, also provide key yet redundant Wnt factors to ISCs ( Baghdadi et al, 2022 ). In case of injury however, these EGCs expand and are critical to efficient intestinal regeneration ( Baghdadi et al, 2022 ). Various types of immune cells also reside in the intestinal mesenchyme and tissue-resident lymphoid cells have been implicated in the regulation of intestinal homeostasis and regeneration by secretion of interleukin factors ( Lindemans et al, 2015 ; Zhu et al, 2019 ).…”

Section: Introductionmentioning

confidence: 99%

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Human Intestinal Organoids: Promise and Challenge

Taelman

Dı́az

Guiu

2022

Front. Cell Dev. Biol.

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The study of human intestinal biology in healthy and diseased conditions has always been challenging. Primary obstacles have included limited tissue accessibility, inadequate in vitro maintenance and ethical constrains. The development of three-dimensional organoid cultures has transformed this entirely. Intestinal organoids are self-organized three-dimensional structures that partially recapitulate the identity, cell heterogeneity and cell behaviour of the original tissue in vitro. This includes the capacity of stem cells to self-renew, as well as to differentiate towards major intestinal lineages. Therefore, over the past decade, the use of human organoid cultures has been instrumental to model human intestinal development, homeostasis, disease, and regeneration. Intestinal organoids can be derived from pluripotent stem cells (PSC) or from adult somatic intestinal stem cells (ISC). Both types of organoid sources harbour their respective strengths and weaknesses. In this mini review, we describe the applications of human intestinal organoids, discussing the differences, advantages, and disadvantages of PSC-derived and ISC-derived organoids.

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Section: Limitations Of Intestinal Organoidsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Human Intestinal Organoids: Promise and Challenge

Taelman

Dı́az

Guiu

2022

Front. Cell Dev. Biol.

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“…Sox10, Plp1, S100b and GFAP are useful markers that help to identify enteric glia, but these proteins are not expressed by all glial subtypes and hint at the plasticity of the different phenotypes. Indeed, this was well-highlighted in a recent study that showed that GFAP+ cells arise from Plp1+ glia and support the intestinal stem cell niche by providing Wnt ligands [ 197 ]. The authors demonstrated that ablation of the GFAP+ population in mice leads to a transient disruption of epithelial homeostasis and that the GFAP+ cell pool is replenished by Plp1+ cells.…”

Section: Schwann Cell Involvement In Physiology and Disorders Of The ...mentioning

confidence: 99%

“…The authors demonstrated that ablation of the GFAP+ population in mice leads to a transient disruption of epithelial homeostasis and that the GFAP+ cell pool is replenished by Plp1+ cells. Furthermore, GFAP+ glia support intestinal regeneration in a paracrine way [ 197 ] and thus could represent an ‘activated’ state of the ENS glia, similar to the activated SCs seen in regeneration of the skin and digit tip [ 44 , 45 , 47 ].…”

Section: Schwann Cell Involvement In Physiology and Disorders Of The ...mentioning

confidence: 99%

Schwann Cells in Digestive System Disorders

Goluba

Kunrade

Riekstiņa

et al. 2022

Cells

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Proper functioning of the digestive system is ensured by coordinated action of the central and peripheral nervous systems (PNS). Peripheral innervation of the digestive system can be viewed as intrinsic and extrinsic. The intrinsic portion is mainly composed of the neurons and glia of the enteric nervous system (ENS), while the extrinsic part is formed by sympathetic, parasympathetic, and sensory branches of the PNS. Glial cells are a crucial component of digestive tract innervation, and a great deal of research evidence highlights the important status of ENS glia in health and disease. In this review, we shift the focus a bit and discuss the functions of Schwann cells (SCs), the glial cells of the extrinsic innervation of the digestive system. For more context, we also provide information on the basic findings regarding the function of innervation in disorders of the digestive organs. We find diverse SC roles described particularly in the mouth, the pancreas, and the intestine. We note that most of the scientific evidence concerns the involvement of SCs in cancer progression and pain, but some research identifies stem cell functions and potential for regenerative medicine.

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Deep into the niche: Deciphering local endoderm‐microenvironment interactions in development, homeostasis, and disease of pancreas and intestine

et al. 2023

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Unraveling molecular and functional heterogeneity of niche cells within the developing endoderm could resolve mechanisms of tissue formation and maturation. Here, we discuss current unknowns in molecular mechanisms underlying key developmental events in pancreatic islet and intestinal epithelial formation. Recent breakthroughs in single‐cell and spatial transcriptomics, paralleled with functional studies in vitro, reveal that specialized mesenchymal subtypes drive the formation and maturation of pancreatic endocrine cells and islets via local interactions with epithelium, neurons, and microvessels. Analogous to this, distinct intestinal niche cells regulate both epithelial development and homeostasis throughout life. We propose how this knowledge can be used to progress research in the human context using pluripotent stem cell‐derived multilineage organoids. Overall, understanding the interactions between the multitude of microenvironmental cells and how they drive tissue development and function could help us make more therapeutically relevant in vitro models.

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Enteric glial cell heterogeneity regulates intestinal stem cell niches

Cited by 61 publications

References 68 publications

Human Intestinal Organoids: Promise and Challenge

Human Intestinal Organoids: Promise and Challenge

Schwann Cells in Digestive System Disorders

Deep into the niche: Deciphering local endoderm‐microenvironment interactions in development, homeostasis, and disease of pancreas and intestine

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