High-resolution transcriptional and morphogenetic profiling of cells from micropatterned human ESC gastruloid cultures

Minn, Kyaw Thu; Fu, Yaotian; He, Shenghua; Dietmann, Sabine; George, Steven C.; Anastasio, Mark A.; Morris, Samantha A.; Solnica‐Krezel, Lilianna

doi:10.7554/elife.59445

Cited by 84 publications

(119 citation statements)

References 96 publications

(205 reference statements)

Supporting

Mentioning

109

Contrasting

Order By: Relevance

“…Consequently, this highly reproducible model is an optimal tool to investigate the molecular mechanisms controlling the self-organization potential of hPSCs. In future, its reproducibility will also call the attention of pharmacologist to deploying this embryoid model in target identification and drug discovery studies [ 11 , 20 , 93 , 112 , 113 , 114 , 115 , 116 , 117 , 118 ].…”

Section: Human Embryoidsmentioning

confidence: 99%

Human Embryo Models and Drug Discovery

Rosner¹,

Reithofer²,

Fink³

et al. 2021

IJMS

View full text Add to dashboard Cite

For obvious reasons, such as, e.g., ethical concerns or sample accessibility, model systems are of highest importance to study the underlying molecular mechanisms of human maladies with the aim to develop innovative and effective therapeutic strategies. Since many years, animal models and highly proliferative transformed cell lines are successfully used for disease modelling, drug discovery, target validation, and preclinical testing. Still, species-specific differences regarding genetics and physiology and the limited suitability of immortalized cell lines to draw conclusions on normal human cells or specific cell types, are undeniable shortcomings. The progress in human pluripotent stem cell research now allows the growth of a virtually limitless supply of normal and DNA-edited human cells, which can be differentiated into various specific cell types. However, cells in the human body never fulfill their functions in mono-lineage isolation and diseases always develop in complex multicellular ecosystems. The recent advances in stem cell-based 3D organoid technologies allow a more accurate in vitro recapitulation of human pathologies. Embryoids are a specific type of such multicellular structures that do not only mimic a single organ or tissue, but the entire human conceptus or at least relevant components of it. Here we briefly describe the currently existing in vitro human embryo models and discuss their putative future relevance for disease modelling and drug discovery.

show abstract

Section: Human Embryoidsmentioning

confidence: 99%

Human Embryo Models and Drug Discovery

Rosner¹,

Reithofer²,

Fink³

et al. 2021

IJMS

View full text Add to dashboard Cite

show abstract

“…[47][48][49] Transcriptional and morphogenetic profiling showed that extra-embryonic ectoderm (ExE)-like cells were generated within this model, which indicated the expression of TE and amnion specific genes. [50] A recent study on this system revealed that the specification of all the three germ layers with a TE layer www.advancedsciencenews.com www.advancedscience.com could be achieved with a timely exposure to Wnt, BMP, and/or Nodal and that there exists coordination between different signaling pathways to regulate the different tissue specification. [51] Recently, hESCs grown as suspension cultures on non-adherent plates with Chir, gave rise to compact elongated structures, called human gastruloids, that spatiotemporally resembled human gastrulation.…”

Section: Human Peri-and Post-implantation Modelsmentioning

confidence: 99%

From Snapshots to Development: Identifying the Gaps in the Development of Stem Cell‐based Embryo Models along the Embryonic Timeline

et al. 2021

View full text Add to dashboard Cite

In recent years, stem cell-based models that reconstruct mouse and human embryogenesis have gained significant traction due to their near-physiological similarity to natural embryos. Embryo models can be generated in large numbers, provide accessibility to a variety of experimental tools such as genetic and chemical manipulation, and confer compatibility with automated readouts, which permits exciting experimental avenues for exploring the genetic and molecular principles of self-organization, development, and disease. However, the current embryo models recapitulate only snapshots within the continuum of embryonic development, allowing the progression of the embryonic tissues along a specific direction. Hence, to fully exploit the potential of stem cell-based embryo models, multiple important gaps in the developmental landscape need to be covered. These include recapitulating the lesser-explored interactions between embryonic and extraembryonic tissues such as the yolk sac, placenta, and the umbilical cord; spatial and temporal organization of tissues; and the anterior patterning of embryonic development. Here, it is detailed how combinations of stem cells and versatile bioengineering technologies can help in addressing these gaps and thereby extend the implications of embryo models in the fields of cell biology, development, and regenerative medicine.

show abstract

“…Here we visualize and quantitatively measure the levels of endogenous Nodal and Lefty1/2 mRNA and protein in a model of human germ layer patterning, micropatterned human embryonic stem cells (hESCs)-based gastruloids (15,16). In this model, exogenous BMP signaling triggers a cascade of signaling through the BMP, Wnt, and Nodal pathways causing germ layer differentiation.…”

Section: Introductionmentioning

confidence: 99%

Nodal is a short-range morphogen with activity that spreads through a relay mechanism in human gastruloids

Liu

Nemashkalo

Jung

et al. 2021

Preprint

View full text Add to dashboard Cite

Morphogens are signaling molecules that convey positional information and dictate cell fates during development. Little is known about how morphogen gradients are created and interpreted during mammalian embryogenesis. Here we take advantage of a human gastruloid model to visualize endogenous Nodal protein in living cells. We show that Nodal is extremely short range so that Nodal protein is limited to the immediate neighborhood of source cells. Nodal activity spreads through a relay mechanism in which Nodal production induces neighboring cells to transcribe Nodal. We further show that the Nodal inhibitor Lefty, while biochemically capable of long-range diffusion, also acts locally to control the timing of Nodal spread and therefore of mesoderm differentiation during patterning. Our study establishes a novel paradigm for tissue patterning by an activator-inhibitor pair.

show abstract

High-resolution transcriptional and morphogenetic profiling of cells from micropatterned human ESC gastruloid cultures

Cited by 84 publications

References 96 publications

Human Embryo Models and Drug Discovery

Human Embryo Models and Drug Discovery

From Snapshots to Development: Identifying the Gaps in the Development of Stem Cell‐based Embryo Models along the Embryonic Timeline

Nodal is a short-range morphogen with activity that spreads through a relay mechanism in human gastruloids

Contact Info

Product

Resources

About