Individual variation in the emergence of anterior-to-posterior neural fates from human pluripotent stem cells.
Stem Cell Reports
; 19(9): 1336-1350, 2024 Sep 10.
Article
en En
| MEDLINE
| ID: mdl-39151428
ABSTRACT
Variability between human pluripotent stem cell (hPSC) lines remains a challenge and opportunity in biomedicine. In this study, hPSC lines from multiple donors were differentiated toward neuroectoderm and mesendoderm lineages. We revealed dynamic transcriptomic patterns that delineate the emergence of these lineages, which were conserved across lines, along with individual line-specific transcriptional signatures that were invariant throughout differentiation. These transcriptomic signatures predicted an antagonism between SOX21-driven forebrain fates and retinoic acid-induced hindbrain fates. Replicate lines and paired adult tissue demonstrated the stability of these line-specific transcriptomic traits. We show that this transcriptomic variation in lineage bias had both genetic and epigenetic origins, aligned with the anterior-to-posterior structure of early mammalian development, and was present across a large collection of hPSC lines. These findings contribute to developing systematic analyses of PSCs to define the origin and consequences of variation in the early events orchestrating individual human development.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Diferenciación Celular
/
Linaje de la Célula
/
Células Madre Pluripotentes
/
Transcriptoma
Límite:
Humans
Idioma:
En
Revista:
Stem Cell Reports
Año:
2024
Tipo del documento:
Article
País de afiliación:
Estados Unidos