Molecular architecture of lineage allocation and tissue organization in early mouse embryo

Peng, Guangdun; Suo, Shengbao; Cui, Guizhong; Yu, Fang; Wang, Ran; Chen, Jun; Chen, Shirui; Liu, Zhiwen; Chen, Guoyu; Qian, Yun; Tam, Patrick; Han, Jing‐Dong J.; Jing, Naihe

doi:10.1038/s41586-019-1469-8

Cited by 192 publications

(254 citation statements)

References 54 publications

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“…For example, Sp1 −/− mouse embryos are retarded in development (Marin et al , ). While we revised this manuscript, Sp1 was identified as an important factor for lineage specification during mouse gastrulation and Sp1 knockout in mESCs facilitated the exit of naïve pluripotency (Peng et al , ), corroborating our findings. Nr5a2 plays a critical role at later stages of neural development (Stergiopoulos & Politis, ).…”

Section: Discussionsupporting

confidence: 79%

“…Notably, the specification of different regions of the mouse epiblast from E6.5 onwards was asynchronous as some sections retained a more undifferentiated character as revealed by projection on our PC1–PC2 map (Fig EV1D–F). Thus, in vitro differentiation to endoderm, mesoderm, and ectoderm recapitulated in vivo germ layer specification: (i) the in vitro endoderm differentiation resembling primitive streak formation, (ii) the in vitro mesoderm differentiation resembling proximal embryonic mesoderm, and (iii) the in vitro ectoderm differentiation resembling the ectoderm specification from the anterior epiblast (Peng et al , ).…”

Section: Resultsmentioning

confidence: 99%

“… AProjection on PC1 and PC2 of gene expression profiles during mESC differentiation to endoderm, mesoderm, and ectoderm and of mESCs with low Nanog expression levels. B–FProjection on PC1 and PC2 of transcriptomes of spatially defined regions of mouse embryos at E5.5 (B), E6.0 (C), E6.5 (D), E7.0 (E), and E7.5 (F) stages (data from Peng et al , ). Corresponding embryo regions are indicated according to the color codes in the inset.…”

Section: Resultsmentioning

confidence: 99%

“…This is consistent with the regionalization of the epiblast into different progenitors of the germ layers (Tam & Behringer, ). Notably, ectoderm is specified from the anterior epiblast (Tam & Behringer, ), which never transits through a primitive streak‐like state (Peng et al , ). Overall, in vitro germ layer differentiation mirrored remarkably lineage specification in vivo .…”

Section: Discussionmentioning

confidence: 99%

“…Molecular Systems Biology 15: e9043 | 2019 embryonic mesoderm, and (iii) the in vitro ectoderm differentiation resembling the ectoderm specification from the anterior epiblast (Peng et al, 2019).…”

mentioning

confidence: 99%

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A gene regulatory network controls the balance between mesendoderm and ectoderm at pluripotency exit

Sladitschek

Neveu

2019

Molecular Systems Biology

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During embryogenesis, differentiation of pluripotent cells into somatic cell types depends both on signaling cues and intrinsic gene expression programs. While the molecular underpinnings of pluripotency are well mapped, much less is known on how mouse embryonic stem cells (mESCs) differentiate. Using RNA‐Seq profiling during specification to the three germ layers, we showed that mESCs switched on condition‐specific gene expression programs from the onset of the differentiation procedure and that primed pluripotency did not constitute an obligatory intermediate state. After inferring the gene network controlling mESC differentiation, we tested the role of the highly connected nodes by deleting them in a triple knock‐in Sox1‐Brachyury‐Eomes mESC line reporting on ectoderm, mesoderm, and endoderm fates. This led to the identification of regulators of mESC differentiation that acted at several levels: Sp1 as a global break on differentiation, Nr5a2 controlling ectoderm specification, and notably Fos:Jun and Zfp354c as opposite switches between ectoderm and mesendoderm fate.

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Section: Discussionsupporting

confidence: 79%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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A gene regulatory network controls the balance between mesendoderm and ectoderm at pluripotency exit

Sladitschek

Neveu

2019

Molecular Systems Biology

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Chemical Cocktail Induces Hematopoietic Reprogramming and Expands Hematopoietic Stem/Progenitor Cells

et al. 2019

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Generation of hematopoietic stem/progenitor cells (HSPCs) via cell expansion or cell reprogramming has been widely achieved by overexpression of transcription factors. Herein, it is reported that without introducing exogenous genes, mouse fibroblasts can be reprogrammed into hemogenic cells based on lineage tracing analysis, which further develop into hematopoietic cells, by treatment of cocktails of chemical compounds. The chemical cocktails also reprogram differentiated hematopoietic cells back into HSPC‐like cells. Most importantly, the chemical cocktails enabling hematopoietic reprogramming robustly promote HSPC proliferation ex vivo. The expanded HSPCs acquire enhanced capacity of hematopoietic reconstruction in vivo. Single‐cell sequencing analysis verifies the expansion of HSPCs and the cell reprogramming toward potential generation of HSPCs at the same time by the chemical cocktail treatment. Thus, the proof‐of‐concept findings not only demonstrate that hematopoietic reprogramming can be achieved by chemical compounds but also provide a promising strategy for acquisition of HSPCs by chemical cocktail‐enabled double effects.

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

et al. 2021

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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.

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Molecular architecture of lineage allocation and tissue organization in early mouse embryo

Cited by 192 publications

References 54 publications

A gene regulatory network controls the balance between mesendoderm and ectoderm at pluripotency exit

A gene regulatory network controls the balance between mesendoderm and ectoderm at pluripotency exit

Chemical Cocktail Induces Hematopoietic Reprogramming and Expands Hematopoietic Stem/Progenitor Cells

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

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