Genome biology · 2025
CLDN10-driven lineage decision in an amnion and primordial germ cell progenitor at the amnion-epiblast boundary in primates.
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Sekulovski Nikola, Carleton Amber E, Rengarajan Anusha, Lin Chien-Wei, Kabir Maliha, Juga Lauren N, Whorton Allison E, Elberfeld Lauren E, Wettstein Jenna C, Schmidt Jenna K, Golos Thaddeus G, Taniguchi Kenichiro
Аннотация
BACKGROUND: A growing body of evidence from primate embryos as well as in vitro systems supports the notion that amnion and primordial germ cell (PGC) lineage progressing cells share a common precursor.
RESULTS: To gain comprehensive transcriptomic insights into this critical but poorly understood precursor and its progeny, we examine the evolving transcriptome of a developing human pluripotent stem cell-derived model of amnion and PGC formation at the single cell level. This analysis reveals several continuous amniotic fate progressing states with state-specific markers. Additionally, a progenitor-like cell, that displays bi-potential characteristics for amnion and PGC-like cell lineages and is marked by CLDN10, is identified. Strikingly, we find that expression of CLDN10 is restricted to the amnion-epiblast boundary region in our human post-implantation amniotic sac model as well as in peri-gastrula cynomolgus macaque embryos; moreover, this boundary region presents amnion and PGC progenitor-like transcriptional characteristics. Furthermore, our loss of function analysis shows that CLDN10 promotes amniotic but suppresses PGC-like fate.
CONCLUSIONS: Overall, based on the single cell transcriptomic resource in this study, we identify a CLDN10+ amnion and PGC progenitor-like population at the amnion-epiblast boundary of the primate peri-gastrula, and present additional molecular clues as to how amnion and PGC may be formed at the amnion-epiblast boundary in human peri-gastrula.
RESULTS: To gain comprehensive transcriptomic insights into this critical but poorly understood precursor and its progeny, we examine the evolving transcriptome of a developing human pluripotent stem cell-derived model of amnion and PGC formation at the single cell level. This analysis reveals several continuous amniotic fate progressing states with state-specific markers. Additionally, a progenitor-like cell, that displays bi-potential characteristics for amnion and PGC-like cell lineages and is marked by CLDN10, is identified. Strikingly, we find that expression of CLDN10 is restricted to the amnion-epiblast boundary region in our human post-implantation amniotic sac model as well as in peri-gastrula cynomolgus macaque embryos; moreover, this boundary region presents amnion and PGC progenitor-like transcriptional characteristics. Furthermore, our loss of function analysis shows that CLDN10 promotes amniotic but suppresses PGC-like fate.
CONCLUSIONS: Overall, based on the single cell transcriptomic resource in this study, we identify a CLDN10+ amnion and PGC progenitor-like population at the amnion-epiblast boundary of the primate peri-gastrula, and present additional molecular clues as to how amnion and PGC may be formed at the amnion-epiblast boundary in human peri-gastrula.