{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T12:41:36Z","timestamp":1790772096514,"version":"4.1.0"},"reference-count":66,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2025,9,27]],"date-time":"2025-09-27T00:00:00Z","timestamp":1758931200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institute of Health","award":["R35DE034348"],"award-info":[{"award-number":["R35DE034348"]}]}],"content-domain":{"domain":["www.mdpi.com"],"crossmark-restriction":true},"short-container-title":["IJMS"],"abstract":"<jats:p>The growth plate is a specialized cartilage structure near the ends of long bones that orchestrates longitudinal bone growth during fetal and postnatal stages. Within this region reside a dynamic population of growth plate skeletal stem cells (gpSSCs), primarily located in the resting zone, which possess self-renewal and multilineage differentiation capacity. Recent advances in cell-lineage tracing, single-cell transcriptomics, and in vivo functional studies have revealed distinct subpopulations of gpSSCs, which are defined by markers such as parathyroid hormone-related protein (PTHrP), CD73, axis inhibition protein 2 (Axin2), forkhead box protein A2 (FoxA2), and apolipoprotein E (ApoE). These stem cells interact intricately with their niche, particularly after the formation of the secondary ossification center, through stage-specific regulatory mechanisms involving several key signaling pathways. This review summarizes the current understanding of gpSSC identity, behavior, and regulation, focusing on how these cells sustain growth plate function through adapting to biomechanical and molecular cues.<\/jats:p>","DOI":"10.3390\/ijms26199460","type":"journal-article","created":{"date-parts":[[2025,9,30]],"date-time":"2025-09-30T10:54:48Z","timestamp":1759229688000},"page":"9460","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Growth Plate Skeletal Stem Cells and Their Actions Within the Stem Cell Niche"],"prefix":"10.3390","volume":"26","author":[{"given":"Natalie Kiat-amnuay","family":"Cheng","sequence":"first","affiliation":[{"name":"Department of Diagnostic and Biomedical Sciences, School of Dentistry, The University of Texas Health Science Center at Houston (UTHealth Houston), Houston, TX 77054, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4226-7358","authenticated-orcid":false,"given":"Shion","family":"Orikasa","sequence":"additional","affiliation":[{"name":"Department of Diagnostic and Biomedical Sciences, School of Dentistry, The University of Texas Health Science Center at Houston (UTHealth Houston), Houston, TX 77054, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3771-8230","authenticated-orcid":false,"given":"Noriaki","family":"Ono","sequence":"additional","affiliation":[{"name":"Department of Diagnostic and Biomedical Sciences, School of Dentistry, The University of Texas Health Science Center at Houston (UTHealth Houston), Houston, TX 77054, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"598","DOI":"10.1016\/j.cell.2008.01.038","article-title":"Stem Cells and Niches: Mechanisms That Promote Stem Cell Maintenance throughout Life","volume":"132","author":"Morrison","year":"2008","journal-title":"Cell"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1016\/S0092-8674(00)81692-X","article-title":"Stem Cells: Units of Development, Units of Regeneration, and Units in Evolution","volume":"100","author":"Weissman","year":"2000","journal-title":"Cell"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1016\/j.cell.2013.07.004","article-title":"The Intestinal Crypt, A Prototype Stem Cell Compartment","volume":"154","author":"Clevers","year":"2013","journal-title":"Cell"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/j.cell.2018.07.029","article-title":"Identification of the Human Skeletal Stem Cell","volume":"175","author":"Chan","year":"2018","journal-title":"Cell"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1016\/j.cell.2008.01.025","article-title":"Hematopoiesis: An Evolving Paradigm for Stem Cell Biology","volume":"132","author":"Orkin","year":"2008","journal-title":"Cell"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1038\/s41586-018-0662-5","article-title":"Resting zone of the growth plate houses a unique class of skeletal stem cells","volume":"563","author":"Mizuhashi","year":"2018","journal-title":"Nature"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1038\/s41586-019-0989-6","article-title":"A radical switch in clonality reveals a stem cell niche in the epiphyseal growth plate","volume":"567","author":"Newton","year":"2019","journal-title":"Nature"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1023","DOI":"10.1242\/dev.102210","article-title":"Skeletal stem cells","volume":"142","author":"Bianco","year":"2015","journal-title":"Development"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"R1","DOI":"10.1530\/JOE-20-0045","article-title":"Home for a rest: Stem cell niche of the postnatal growth plate","volume":"246","author":"Lui","year":"2020","journal-title":"J. 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