Regeneration of the human segmentation clock in somitoids in vitro.
EMBO J
; 41(23): e110928, 2022 12 01.
Article
in En
| MEDLINE
| ID: mdl-36245268
ABSTRACT
Each vertebrate species appears to have a unique timing mechanism for forming somites along the vertebral column, and the process in human remains poorly understood at the molecular level due to technical and ethical limitations. Here, we report the reconstitution of human segmentation clock by direct reprogramming. We first reprogrammed human urine epithelial cells to a presomitic mesoderm (PSM) state capable of long-term self-renewal and formation of somitoids with an anterior-to-posterior axis. By inserting the RNA reporter Pepper into HES7 and MESP2 loci of these iPSM cells, we show that both transcripts oscillate in the resulting somitoids at ~5 h/cycle. GFP-tagged endogenous HES7 protein moves along the anterior-to-posterior axis during somitoid formation. The geo-sequencing analysis further confirmed anterior-to-posterior polarity and revealed the localized expression of WNT, BMP, FGF, and RA signaling molecules and HOXA-D family members. Our study demonstrates the direct reconstitution of human segmentation clock from somatic cells, which may allow future dissection of the mechanism and components of such a clock and aid regenerative medicine.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Somites
/
Mesoderm
Aspects:
Ethics
Limits:
Humans
Language:
En
Journal:
EMBO J
Year:
2022
Document type:
Article