Cranioencephalic functional lymphoid units in glioblastoma DOI Creative Commons
Celia Dobersalske, Laurèl Rauschenbach, Yichao Hua

et al.

Nature Medicine, Journal Year: 2024, Volume and Issue: 30(10), P. 2947 - 2956

Published: July 31, 2024

The ecosystem of brain tumors is considered immunosuppressed, but our current knowledge may be incomplete. Here we analyzed clinical cell and tissue specimens derived from patients presenting with glioblastoma or nonmalignant intracranial disease to report that the cranial bone (CB) marrow, in juxtaposition treatment-naive tumors, harbors active lymphoid populations at time initial diagnosis. Clinical anatomical imaging, single-cell molecular immune profiling quantification tumor reactivity identified CD8

Language: Английский

Human blastoids model blastocyst development and implantation DOI Creative Commons
Harunobu Kagawa, Alok Javali, Heidar Heidari Khoei

et al.

Nature, Journal Year: 2021, Volume and Issue: 601(7894), P. 600 - 605

Published: Dec. 2, 2021

Abstract One week after fertilization, human embryos implant into the uterus. This event requires embryo to form a blastocyst consisting of sphere encircling cavity lodging proper. Stem cells can model that we called blastoid 1 . Here show naive pluripotent stem cultured in PXGL medium 2 and triply inhibited for Hippo, TGF-β ERK pathways efficiently (with more than 70% efficiency) blastoids generating blastocyst-stage analogues three founding lineages (more 97% trophectoderm, epiblast primitive endoderm) according sequence timing development. Blastoids spontaneously first axis, observe induces local maturation polar thereby endowing with capacity directionally attach hormonally stimulated endometrial cells, as during implantation. Thus, propose such is faithful, scalable ethical investigating implantation development 3,4

Language: Английский

Citations

327

Early human embryonic development: Blastocyst formation to gastrulation DOI Creative Commons
Janet Rossant, Patrick Tam

Developmental Cell, Journal Year: 2022, Volume and Issue: 57(2), P. 152 - 165

Published: Jan. 1, 2022

Language: Английский

Citations

132

Complete human day 14 post-implantation embryo models from naive ES cells DOI Creative Commons
Bernardo Oldak,

Emilie Wildschutz,

Vladyslav Bondarenko

et al.

Nature, Journal Year: 2023, Volume and Issue: unknown

Published: Sept. 6, 2023

The ability to study human post-implantation development remains limited owing ethical and technical challenges associated with intrauterine after implantation1. Embryo-like models spatially organized morphogenesis structure of all defining embryonic extra-embryonic tissues the conceptus (that is, disc, bilaminar yolk sac, chorionic sac surrounding trophoblast layer) remain lacking1,2. Mouse naive stem cells have recently been shown give rise capable self-assembling into post-gastrulation structured stem-cell-based embryo (called SEMs)3. Here we extend those findings humans using only genetically unmodified (cultured in enhanced cell medium conditions)4. Such fully integrated complete SEMs recapitulate organization nearly known lineages compartments embryos, including epiblast, hypoblast, mesoderm layer latter compartments. These demonstrated developmental growth dynamics that resemble key hallmarks stage embryogenesis up 13-14 days fertilization (Carnegie 6a). include disc formation, epiblast lumenogenesis, polarized amniogenesis, anterior-posterior symmetry breaking, primordial germ-cell specification, visceral parietal endoderm expansion defines a cavity connecting stalk, trophoblast-surrounding compartment demonstrating syncytium lacunae formation. This SEM platform will probably enable experimental investigation previously inaccessible windows early post implantation peri-gastrulation development.

Language: Английский

Citations

109

Single-cell technologies: From research to application DOI
Lu Wen, Guoqiang Li, Tao Huang

et al.

The Innovation, Journal Year: 2022, Volume and Issue: 3(6), P. 100342 - 100342

Published: Oct. 18, 2022

Language: Английский

Citations

87

Stage-specific H3K9me3 occupancy ensures retrotransposon silencing in human pre-implantation embryos DOI Creative Commons
Ruimin Xu, Sen Li, Qiu Wu

et al.

Cell stem cell, Journal Year: 2022, Volume and Issue: 29(7), P. 1051 - 1066.e8

Published: July 1, 2022

Language: Английский

Citations

72

3D-cultured blastoids model human embryogenesis from pre-implantation to early gastrulation stages DOI Creative Commons
Rowan M. Karvas, Joseph E. Zemke,

Syed Shahzaib Ali

et al.

Cell stem cell, Journal Year: 2023, Volume and Issue: 30(9), P. 1148 - 1165.e7

Published: Sept. 1, 2023

Naive human pluripotent stem cells have the remarkable ability to self-organize into blastocyst-like structures ("blastoids") that model lineage segregation in pre-implantation embryo. However, extent which blastoids can recapitulate defining features of post-implantation development remains unexplored. Here, we report cultured on thick three-dimensional (3D) extracellular matrices capture hallmarks early development, including epiblast lumenogenesis, rapid expansion and diversification trophoblast lineages, robust invasion extravillous by day 14. Extended blastoid culture results localized activation primitive streak marker TBXT emergence embryonic germ layers 21. We also show modulation WNT signaling alters balance between fates blastoids. This work demonstrates 3D-cultured offer a continuous integrated vitro system extraembryonic from gastrulation stages.

Language: Английский

Citations

57

Human embryo implantation DOI Creative Commons
Joanne Muter, Vincent J. Lynch, Rajiv C. McCoy

et al.

Development, Journal Year: 2023, Volume and Issue: 150(10)

Published: May 15, 2023

Embryo implantation in humans is interstitial, meaning the entire conceptus embeds endometrium before placental trophoblast invades beyond uterine mucosa into underlying inner myometrium. Once implanted, embryo survival pivots on transformation of an anti-inflammatory bed, termed decidua, under homeostatic control natural killer cells. Here, we examine evolutionary context and elaborate remodelling after conception humans. We also discuss interactions between decidualising that regulate interstitial determine fitness. Together, this Review highlights precarious but adaptable nature process.

Language: Английский

Citations

54

Epigenetic regulation of early human embryo development DOI Creative Commons
Amy L. Wilkinson, Irene Zorzan, Peter J. Rugg‐Gunn

et al.

Cell stem cell, Journal Year: 2023, Volume and Issue: 30(12), P. 1569 - 1584

Published: Oct. 18, 2023

Studies of mammalian development have advanced our understanding the genetic, epigenetic, and cellular processes that orchestrate embryogenesis uncovered new insights into unique aspects human embryogenesis. Recent studies now produced first epigenetic maps early embryogenesis, stimulating ideas about reprogramming, cell fate control, potential mechanisms underpinning developmental plasticity in embryos. In this review, we discuss these regulation importance for safeguarding development. We also highlight unanswered questions key challenges remain to be addressed.

Language: Английский

Citations

45

A Comprehensive Human Embryogenesis Reference Tool using Single-Cell RNA-Sequencing Data DOI Open Access
Cheng Zhao, Álvaro Plaza Reyes,

John P. Schell

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2021, Volume and Issue: unknown

Published: May 7, 2021

Summary Stem cell-based embryo models offer unprecedented experimental tools for studying early human development. The usefulness of hinges on their molecular, cellular and structural fidelities to in vivo counterparts. To authenticate models, single-cell RNA-sequencing has been utilised unbiased transcriptional profiling. However, a well-organised integrated dataset, serving as universal reference benchmarking remains unavailable. Herein, we developed such reference, through integration six published datasets covering developmental stages from the zygote gastrula. Lineage annotations are contrasted validated with available non-human primate datasets. Using stabilised UMAP constructed web tool, where query can be projected annotated predicted cell identities. this examined several recent highlighting risk misannotation when relevant references lacking.

Language: Английский

Citations

66

The exploration of pluripotency space: Charting cell state transitions in peri-implantation development DOI Creative Commons
Martín F. Pera, Janet Rossant

Cell stem cell, Journal Year: 2021, Volume and Issue: 28(11), P. 1896 - 1906

Published: Oct. 22, 2021

Language: Английский

Citations

62