Advancing insights into stem cell niche complexities with next-generation technologies
Open accessAbstract
Adult tissue-specific stem cells are essential for homeostatic tissue maintenance and key to regeneration during injury repair or disease. Many critical stem cell functions rely on the presence of well-timed cues from the microenvironment or niche, which includes a diverse range of components, including neuronal, circulating and extracellular matrix inputs as well as an array of neighboring niche cells directly interacting with the stem cells. However, studies of stem cells and their niche have been challenging due to the complexity of adult stem cell functions, their intrinsic controls and the multiple regulatory niche components. Here, we review recent major advances in our understanding of the complex interplay between stem cells and their niche that were enabled by the tremendous technological leaps in single-cell transcriptome analyses, 3D in vitro cultures and 4D in vivo microscopy of stem cell niches.
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Culture systems containing epidermal and dermal cells have been used to model human skin outside of the body for research or clinical uses for over 40 years.
“Culture systems containing epidermal and dermal cells have been used to model human skin outside of the body for research or clinical uses for over 40 years7,8,10; however, growing functional skin appendages in these systems has been persistently difficult.”
From Hair-bearing human skin generated entirely from pluripotent stem cells (2020) · cites this paper as [8]
The “Modeling complexity” section (page unavailable) describes cultured epidermal and dermal clusters as a skin model, supporting the general point that these cells have been used in culture. Its example uses mouse cells, however, and our copy does not establish use to model human skin for over 40 years or for clinical purposes. (LLM, conf=0.83)
Experimental — accuracy not yet measuredReconstruction of appendage-bearing skin in cultures and in bioengineered grafts remains an unmet biomedical challenge.
“Reconstruction of appendage-bearing skin in cultures and in bioengineered grafts remains an unmet biomedical challenge3–9.”
From Hair-bearing human skin generated entirely from pluripotent stem cells (2020) · cites this paper as [8]
The Modeling complexity section says flat cultures lack tissue complexity and reports that older mouse skin clusters lost the ability to induce hair follicles, although this could be rescued. It also describes murine skin organoids that make hair and sebaceous glands. These passages support limitations in cultured skin reconstruction, but the paper does not address bioengineered skin grafts or characterize their reconstruction as an unmet challenge. (LLM, conf=0.78)
Experimental — accuracy not yet measuredGrowing functional skin appendages in culture systems containing epidermal and dermal cells has been persistently difficult.
“Culture systems containing epidermal and dermal cells have been used to model human skin outside of the body for research or clinical uses for over 40 years7,8,10; however, growing functional skin appendages in these systems has been persistently difficult.”
From Hair-bearing human skin generated entirely from pluripotent stem cells (2020) · cites this paper as [8]
In “Modeling complexity: 2D co-cultures and 3D tissue-recapitulating organoids” (page unavailable), the review says 3D epidermal–dermal clusters from old mouse skin lost the ability to induce hair follicles, although that ability could be rescued. This supports a difficulty in a particular culture system, but does not establish that growing functional skin appendages has been persistently difficult across the skin culture systems described in the claim; the review also describes murine organoids capable of making hair and sebaceous glands. (LLM, conf=0.78)
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Self-citationMacrophages Contribute to the Cyclic Activation of Adult Hair Follicle Stem Cells
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Stretching the limits: from homeostasis to stem cell plasticity in wound healing and cancer
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Imaging organoids: a bright future ahead
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The road ended up at stem cells
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Flagged first, then by citations
1 of the 114 references couldn’t be matched to a known paper.
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Hair-bearing human skin generated entirely from pluripotent stem cells
Lee, J., Rabbani, C. C., Gao, H., Steinhart, M. R., Woodruff, B. M., Pflum, Z. E., Kim, A., Heller, S., Liu, Y., Shipchandler, T. Z., et al. (2020) · Nature · doi:10.1038/s41586-020-2352-3 · Cited by 487 · see citing works
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Self-citationOrganoids to study immune functions, immunological diseases and immunotherapy
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Hair-bearing human skin generated entirely from pluripotent stem cellsPreprint
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The regenerative journey: exploring stem cell roles from injury detection to tissue repair
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A 4D road map for the formation of hair follicles
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Hypoxia Preconditioning of Bone Marrow Mesenchymal Stem Cells Before Implantation in Orthopaedics
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Skin stem cells in health and in disease
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Self-citationMore Than the Sum of Its Parts: Single-Cell Transcriptomics Reveals Epidermal Cell States
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Self-citationBioengineering strategies for regeneration of skin integrity: A literature review
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Skin Organoid Research Progress and Potential Applications
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Spatio-temporal regulation of gene expression defines subpopulations of epidermal stem cells
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Self-citationNext Generation Sequencing and Stem Cells
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Niche cell positioning drives functional heterogeneity in the Drosophila testis stem cell niche
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- Authors
- Heitman, N., Saxena, N., & Rendl, M.
- Affiliations
- Icahn School of Medicine at Mount Sinai (US)
- Corresponding author
- Rendl, Michael
- Venue
- Current Opinion in Cell Biology
- Publisher
- Elsevier BV
- Published
- 2018-12
- Volume
- 55
- Pages
- 87-95
- ISSN
- 0955-0674 (ISSN-L)
- PMC
- PMC6269204
- OpenAlex
- W2884636716
- Cited by
- 31
- References
- 114
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 4 · 2023: 1 · 2022: 1 · 2021: 6 · 2020: 6 · 2019: 4 · 2018: 5
- FWCI
- 0.87
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Current Opinion in Cell Biology (acceptedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- NIH/NIAMS (F30AR070639, R01AR071047, R01AR063151)
- NIH/NIGMS (T32GM007280)
- New York State Department of Health (NYSTEM-C029574)
- Topics
- Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
- Keywords
- stem cell niche, extracellular matrix, niche cells, single-cell transcriptomics, tissue homeostasis, regeneration
- MeSH terms
- Animals, Humans, Models, Biological, Organoids, Imaging, Three-Dimensional, Stem Cell Niche, Stem Cell Research, Single-Cell Analysis
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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