3107 – Multi-Organ Functions of Yolk Sac During Human Early Development

Jardine, Laura; Botting, Rachel A.; Goh, Issac; Rose, Antony; Webb, Simone; Londoño, Mariana Quiroga; Stephenson, Emily; Engelbert, Justin; Roberts, Irene; Göttgens, Berthold; Teichmann, Sarah; Haniffa, Muzlifah

doi:10.1016/j.exphem.2022.07.163

Cited by 1 publication

(6 citation statements)

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“…The above data implicates prenatal skin macrophages as key players in angiogenesis, supporting our earlier observation of pro-angiogenic gene module expression in TMLM in the human yolk sac 99 . We next set out to validate our findings using two distinct cell culture assays.…”

Section: Macrophages Support Prenatal Skin Angiogenesissupporting

confidence: 89%

“…Notably, macrophage subsets appear to play distinct roles in scarless skin repair, fibroblast homeostasis and neurovascular development. This is in part contributed to by yolk-sac derived TMLM 99,140 , which have also been reported in human prenatal testicular cords, suggesting there is a broader tissue distribution in early gestation than previously thought and functions outside of the central nervous system.…”

Section: Discussionmentioning

confidence: 57%

“…We recently identified yolk-sac derived TREM2 + macrophages that share an expression profile with microglia-like macrophages from other developing organs, such as the brain, prenatal skin and gonads [97][98][99] . TREM2 + microglia-like macrophages (TMLM), including those in prenatal skin, expressed P2RY12, CX3CR1, TMEM119, OLFML3, C3 (Extended Data Fig.…”

Section: The Adult Fibroblast Gene Expression Profile ('Immune Activa...mentioning

confidence: 99%

“…We first re-embedded cells into a batch-corrected latent space with a dimension of 30 using scVI model as implemented in scvitools considering donor and chemistry as batches. The model was trained using the 10000 most highly variable genes which were selected based on dispersion (min_mean=0.001, max_mean=10) as previously described 99 . Where FACs correction was applied, we calculated a FACS isolation correction factor for each sample s sorted with gate i as (fs = log(piS/Si))…”

Section: Differential Abundance Analysismentioning

confidence: 99%

“…where pi is the true proportion of cells from gate i and S represents the total number of cells from both gates 99 . A KNN graph of cells was constructed based on distances in the latent space and cells assigned to neighbourhoods using the milopy.core.make_nhoods function (prop=0.1).…”

Section: Differential Abundance Analysismentioning

confidence: 99%

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A human prenatal skin cell atlas reveals immune cell regulation of skin morphogenesis

Gopee,

Huang,

Olabi

et al. 2023

Preprint

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Human prenatal skin is populated by innate immune cells including macrophages, and whether they act solely in immunity or have additional functions in morphogenesis is unclear. We assembled the first comprehensive multi-omic reference atlas of prenatal human skin (7-16 post-conception weeks), combining single cell and spatial transcriptomic data, to characterise the skin's microenvironmental cellular organisation. This revealed that crosstalk between non-immune and immune cells underpins formation of hair follicles, has implications for scarless wound healing, and is critical for skin angiogenesis. We benchmarked a skin organoid model, derived from human embryonic stem (ES) and induced pluripotent stem (iPS) cells, against prenatal and adult skin, demonstrating close recapitulation of the epidermal and dermal skin components during hair follicle development. Notably, the skin organoid lacked immune cells and had markedly diminished endothelial cell heterogeneity and quantity. From our in vivo skin cell atlas data, we found that macrophages and macrophage-derived growth factors play a key role in driving endothelial development prenatally. Indeed, vascular network formation was enhanced following transfer of autologous iPS-derived macrophages into both endothelial cell angiogenesis assays and skin organoid cultures. In summary, innate immune cells moonlight as key players in skin morphogenesis beyond their conventional immune roles, a function they achieve via extensive crosstalk with non-immune cells. Finally, we leveraged our human prenatal skin cell atlas to further our understanding of the pathogenesis of genetic hair and skin disorders.

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Section: Macrophages Support Prenatal Skin Angiogenesissupporting

confidence: 89%

Section: Discussionmentioning

confidence: 57%

Section: The Adult Fibroblast Gene Expression Profile ('Immune Activa...mentioning

confidence: 99%

Section: Differential Abundance Analysismentioning

confidence: 99%

Section: Differential Abundance Analysismentioning

confidence: 99%

See 3 more Smart Citations

A human prenatal skin cell atlas reveals immune cell regulation of skin morphogenesis

Gopee,

Huang,

Olabi

et al. 2023

Preprint

Self Cite

View full text Add to dashboard Cite

show abstract

3107 – Multi-Organ Functions of Yolk Sac During Human Early Development

Cited by 1 publication

References 0 publications

A human prenatal skin cell atlas reveals immune cell regulation of skin morphogenesis

A human prenatal skin cell atlas reveals immune cell regulation of skin morphogenesis

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