Article Craniofacial chondrogenesis in organoids from human stem cell-derived neural crest cells

被引：3

作者：

Foltz, Lauren ^{[1
,4
]}

Avabhrath, Nagashree ^{[1
]}

Lanchy, Jean -Marc ^{[1
]}

Levy, Tyler ^{[2
]}

Possemato, Anthony ^{[2
]}

Ariss, Majd ^{[2
]}

Peterson, Bradley ^{[3
]}

Grimes, Mark ^{[1
]}

机构：

[1] Univ Montana, Ctr Biomol Struct & Dynam, Ctr Struct & Funct Neurosci, Div Biol Sci, Missoula, MT 59812 USA

[2] Cell Signaling Technol, Danvers, MA 01923 USA

[3] Pathol Consultants Western Montana, Missoula, MT USA

[4] UCL, Res Dept Struct & Mol Biol, Div Biosci, Gower St, London WC1E 6BT, England

来源：

ISCIENCE | 2024年 / 27卷 / 04期

关键词：

DECOY SEARCH STRATEGY; EXTRACELLULAR-MATRIX; ARTICULAR-CARTILAGE; GROWTH-FACTOR; IN-VITRO; PROTEIN-PHOSPHORYLATION; ENGINEERED CARTILAGE; SIGNALING PATHWAYS; NASAL CHONDROCYTES; RECEPTOR ALK2;

D O I：

10.1016/j.isci.2024.109585

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Knowledge of cell signaling pathways that drive human neural crest differentiation into craniofacial chondrocytes is incomplete, yet essential for using stem cells to regenerate craniomaxillofacial structures. To accelerate translational progress, we developed a differentiation protocol that generated self -organizing craniofacial cartilage organoids from human embryonic stem cell -derived neural crest stem cells. Histological staining of cartilage organoids revealed tissue architecture and staining typical of elastic cartilage. Protein and post -translational modification (PTM) mass spectrometry and snRNA-seq data showed that chondrocyte organoids expressed robust levels of cartilage extracellular matrix (ECM) components: many collagens, aggrecan, perlecan, proteoglycans, and elastic fibers. We identified two populations of chondroprogenitor cells, mesenchyme cells and nascent chondrocytes, and the growth factors involved in paracrine signaling between them. We show that ECM components secreted by chondrocytes not only create a structurally resilient matrix that defines cartilage, but also play a pivotal autocrine cell signaling role in determining chondrocyte fate.

引用

页数：29