2021
Gene expression dynamics underlying cell fate emergence in 2D micropatterned human embryonic stem cell gastruloids
Abstract: Summary Human embryonic stem cells cultured in 2D micropatterns with BMP4 differentiate into a radial arrangement of germ layers and extraembryonic cells. Single-cell transcriptomes demonstrate generation of cell types transcriptionally similar to their in vivo counterparts in Carnegie stage 7 human gastrula. Time-course analyses indicate sequential differentiation, where the epiblast arises by 12 h between the prospective ectoderm in the center and the cells initiating differ…
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Cited by 44 publications
(32 citation statements)
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“…Using single cell RNA-sequencing, we determine the expression of FGF pathway components including FGFR1 as the main receptor and FGF2, FGF4, and FGF17 as the most highly expressed ligands. Our analysis corroborates previous studies describing expression of FGF2 and FGF17 in human embryos and gastruloids but for the first time recognizes a possible role for FGF4 and includes a broad analysis of genes involved in FGF signaling modulation 25,36 . We find that the FGF4 and FGF17 expression are restricted to the PS-like ring and that knockdown of FGF4 significantly reduces PS-like differentiation, while FGF17 knockdown primarily affects downstream mesoderm differentiation.…”
Section: Introductionsupporting
confidence: 89%
“…Using single cell RNA-sequencing, we determine the expression of FGF pathway components including FGFR1 as the main receptor and FGF2, FGF4, and FGF17 as the most highly expressed ligands. Our analysis corroborates previous studies describing expression of FGF2 and FGF17 in human embryos and gastruloids but for the first time recognizes a possible role for FGF4 and includes a broad analysis of genes involved in FGF signaling modulation 25,36 . We find that the FGF4 and FGF17 expression are restricted to the PS-like ring and that knockdown of FGF4 significantly reduces PS-like differentiation, while FGF17 knockdown primarily affects downstream mesoderm differentiation.…”
Section: Introductionsupporting
confidence: 89%
“…A final related question is the origin of the discrepancies we and others 36 found between the primate (i.e., non-mouse) samples in Fig. 2 and Supp.…”
Section: Discussionmentioning
confidence: 85%
“…These cellular identities were then followed by ectoderm specification (SOX2 + , POU5F1 − , and NANOG − ) emerging at 24H, with endoderm (SOX17 + ) and mesoderm (T + and MESP1 + ) populations being observed at 44H into differentiation. 41 While considerably more rapid than in vivo , the time course growth displayed here followed observed germ layer formation events in development, demonstrating the utility of such models for human developmental studies. 4 Microfluidic model systems have also been used to hPSCs under controlled spatial and biochemical conditions.…”
Section: Engineered Gastrulation Modelssupporting
confidence: 53%
“…Single-cell RNA sequencing results unveiled that additional cell types also emerged within this gastruloid system, including epiblast, trophectoderm, and primordial germ cells. Furthermore, by comparing with mouse and primate embryos, the transcriptomic profile confirmed that these engineered gastruloids recapitulated the primate-specific features of embryogenesis [Minn et al, 2020[Minn et al, , 2021. These gastruloids resembling the spatial tissue development during early embryogenesis pose the question of why cell position has such a strong influence on pattern formations.…”
Section: Discussionmentioning
confidence: 65%
