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A radical switch in clonality reveals a stem cell niche in the epiphyseal growth plate

Artikel i vetenskaplig tidskrift
Författare P. T. Newton
L. Li
B. Y. Zhou
C. Schweingruber
M. Hovorakova
M. Xie
X. Y. Sun
L. Sandhow
A. V. Artemov
E. Ivashkin
S. Suter
V. Dyachuk
Maha El Shahawy
Amel Gritli Linde
T. Bouderlique
J. Petersen
A. Mollbrink
J. Lundeberg
G. Enikolopov
H. Qian
K. Fried
M. Kasper
E. Hedlund
I. Adameyko
L. Savendahl
A. S. Chagin
Publicerad i Nature
Volym 567
Nummer/häfte 7747
Sidor 234-+
ISSN 0028-0836
Publiceringsår 2019
Publicerad vid Institutionen för odontologi
Sidor 234-+
Språk en
Länkar dx.doi.org/10.1038/s41586-019-0989-...
Ämnesord intestinal crypt, mechanisms, expression, polarity, pathway, model, Science & Technology
Ämneskategorier Klinisk medicin

Sammanfattning

Longitudinal bone growth in children is sustained by growth plates, narrow discs of cartilage that provide a continuous supply of chondrocytes for endochondral ossification(1). However, it remains unknown how this supply is maintained throughout childhood growth. Chondroprogenitors in the resting zone are thought to be gradually consumed as they supply cells for longitudinal growth(1,2), but this model has never been proved. Here, using clonal genetic tracing with multicolour reporters and functional perturbations, we demonstrate that longitudinal growth during the fetal and neonatal periods involves depletion of chondroprogenitors, whereas later in life, coinciding with the formation of the secondary ossification centre, chondroprogenitors acquire the capacity for self-renewal, resulting in the formation of large, stable monoclonal columns of chondrocytes. Simultaneously, chondroprogenitors begin to express stem cell markers and undergo symmetric cell division. Regulation of the pool of self-renewing progenitors involves the hedgehog and mammalian target of rapamycin complex 1 (mTORC1) signalling pathways. Our findings indicate that a stem cell niche develops postnatally in the epiphyseal growth plate, which provides a continuous supply of chondrocytes over a prolonged period.

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