Discrimination of Stem Cell Status after Subjecting Cynomolgus Monkey Pluripotent Stem Cells to Naïve Conversion DOI Creative Commons
Arata Honda,

Yoshihiro Kawano,

Haruna Izu

et al.

Scientific Reports, Journal Year: 2017, Volume and Issue: 7(1)

Published: March 28, 2017

Abstract Experimental animal models have played an indispensable role in the development of human induced pluripotent stem cell (iPSC) research. The derivation high-quality (so-called “true naïve state”) iPSCs non-human primates enhances their application and safety for regenerative medicine. Although several attempts been made to convert primate PSCs into a truly state, it is unclear which evaluation methods can discriminate them as being naïve. Here we attempted derive cynomolgus monkey (Cm) ( Macaca fascicularis ) embryonic cells (ESCs) iPSCs. Several characteristics Cm ESCs including colony morphology, appearance naïve-related mRNAs proteins, leukaemia inhibitory factor dependency, mitochondrial respiration were confirmed. Next, generated converted state. Transcriptomic comparison with early embryos elucidated partial achievement (termed naïve-like) conversion. When these subjected vitro neural differentiation, enhanced differentiating capacities observed after naïve-like conversion, but some lines exhibited heterogeneity. difficulty achieving contribution chimeric mouse was also demonstrated. These results suggest that could ameliorate differentiation potential even though they not display true characteristics.

Language: Английский

Derivation of Pluripotent Stem Cells with In Vivo Embryonic and Extraembryonic Potency DOI Creative Commons
Yang Yang, Bei Liu, Jun Xu

et al.

Cell, Journal Year: 2017, Volume and Issue: 169(2), P. 243 - 257.e25

Published: April 1, 2017

Language: Английский

Citations

435
Mouse totipotent stem cells captured and maintained through spliceosomal repression DOI Creative Commons
Hui Shen, Min Yang, Shiyu Li

et al.

Cell, Journal Year: 2021, Volume and Issue: 184(11), P. 2843 - 2859.e20

Published: May 1, 2021

Language: Английский

Citations

150
Stem cells and interspecies chimaeras DOI
Jun Wu, Henry T. Greely, Rudolf Jaenisch

et al.

Nature, Journal Year: 2016, Volume and Issue: 540(7631), P. 51 - 59

Published: Nov. 29, 2016

Language: Английский

Citations

159
Pluripotency and X chromosome dynamics revealed in pig pre-gastrulating embryos by single cell analysis DOI Creative Commons
Priscila Ramos‐Ibeas, Fei Sang, Qifan Zhu

et al.

Nature Communications, Journal Year: 2019, Volume and Issue: 10(1)

Published: Jan. 30, 2019

Abstract High-resolution molecular programmes delineating the cellular foundations of mammalian embryogenesis have emerged recently. Similar analysis human embryos is limited to pre-implantation stages, since early post-implantation are largely inaccessible. Notwithstanding, we previously suggested conserved principles pig and development. For further insight on pluripotent states lineage delineation, analysed at single cell resolution. Here show progressive segregation inner mass trophectoderm in blastocysts, epiblast hypoblast late blastocysts. We that following an emergent short naive signature embryos, there a protracted appearance primed advanced embryonic stages. Dosage compensation with respect X-chromosome females attained via X-inactivation epiblasts. Detailed human-pig comparison basis towards comprehending development foundation for studies stem differentiation interspecies chimeras.

Language: Английский

Citations

116
Inhibition of Apoptosis Overcomes Stage-Related Compatibility Barriers to Chimera Formation in Mouse Embryos DOI Creative Commons
Hideki Masaki,

Megumi Kato‐Itoh,

Yusuke Takahashi

et al.

Cell stem cell, Journal Year: 2016, Volume and Issue: 19(5), P. 587 - 592

Published: Nov. 1, 2016

Language: Английский

Citations

110
Assessment of established techniques to determine developmental and malignant potential of human pluripotent stem cells DOI Creative Commons
Thomas F. Allison, Peter W. Andrews,

Yishai Avior

et al.

Nature Communications, Journal Year: 2018, Volume and Issue: 9(1)

Published: May 9, 2018

Abstract The International Stem Cell Initiative compared several commonly used approaches to assess human pluripotent stem cells (PSC). PluriTest predicts pluripotency through bioinformatic analysis of the transcriptomes undifferentiated cells, whereas, embryoid body (EB) formation in vitro and teratoma vivo provide direct tests differentiation. Here we report that EB assays, analyzed after differentiation under neutral conditions promoting ectoderm, mesoderm, or endoderm lineages, are sufficient potential PSCs. However, by histologic examination TeratoScore, which estimates differential gene expression each tumor, not only measures but also allows insight into a PSC’s malignant potential. Each assays can be predict but, at this stage assay development, provides an assessment potential, both relevant pre-clinical safety

Language: Английский

Citations

110
A critical look: Challenges in differentiating human pluripotent stem cells into desired cell types and organoids DOI

Jonas L. Fowler,

Lay Teng Ang, Kyle M. Loh

et al.

Wiley Interdisciplinary Reviews Developmental Biology, Journal Year: 2019, Volume and Issue: 9(3)

Published: Nov. 19, 2019

Too many choices can be problematic. This is certainly the case for human pluripotent stem cells (hPSCs): they harbor potential to differentiate into hundreds of cell types; yet it highly challenging exclusively hPSCs a single desired type. review focuses on unresolved and fundamental questions regarding hPSC differentiation critiquing identity purity resultant populations. These are timely issues in view fact that hPSC-derived populations have or being transplanted patients over 30 ongoing clinical trials. While vitro protocols purport "mimic development," exact number intermediate steps takes given type vivo remains largely unknown. Consequently, most efforts inevitably generate heterogeneous cellular population, as revealed by single-cell RNA-sequencing other analyses. The presence unwanted types differentiated does not portend well transplantation therapies. provides an impetus precisely control ends-for instance, logically blocking formation overexpressing lineage-specifying transcription factors-or harnessing technologies selectively purify types. Conversely, approaches three-dimensional "organoids" from intentionally this intended mimic rich diversity developing tissues, whether all such organoids spatially organized manner akin native organs (and thus, fully qualify organoids) resolved. article categorized under: Adult Stem Cells > Tissue Renewal Regeneration: Cell Differentiation Reversion Gene Expression Transcriptional Hierarchies: Cellular Early Embryonic Development: Gastrulation Neurulation.

Language: Английский

Citations

62
A Technology Roadmap for Innovative Approaches to Kidney Replacement Therapies DOI Open Access
Joseph V. Bonventre, Frank P. Hurst,

Melissa West

et al.

Clinical Journal of the American Society of Nephrology, Journal Year: 2019, Volume and Issue: 14(10), P. 1539 - 1547

Published: Sept. 27, 2019

The number of patients dialyzed for ESKD exceeds 500,000 in the United States and more than 2.6 million people worldwide, with expectation that worldwide will double by 2030. human cost health societal financial is substantial. Dialytic therapy associated an unacceptably high morbidity mortality rate poor quality life. Although innovation many areas science has been transformative, there little dialysis or alternatives kidney replacement (KRT) since its introduction approximately 70 years ago. Advances biology, stem cells cell differentiation protocols, biomaterials, sensors, nano/microtechnology, sorbents engineering, interdisciplinary approaches collaborations can lead to disruptive innovation. Kidney Health Initiative, a public-private partnership between American Society Nephrology US Food Drug Administration, convened multidisciplinary group create technology roadmap innovative KRT address patients' needs. Roadmap living document. It identifies design criteria must be considered replace myriad functions kidney, as well scientific, technical, regulatory, payor milestones required commercialize provide patient access alternatives. Various embodiments potential solutions are discussed, but agnostic any particular solution set. System enablers identified, including vascular access, biomaterial development, biologic immunologic modulation, function, safety monitoring. Important supporting activities include regulatory alignment incentives payment pathways. provides estimated timelines specific so conceptualized ways actionable attract talented innovators from multiple disciplines. used guide selection KidneyX prizes KRT.

Language: Английский

Citations

59
Characterizing Cellular Differentiation Potency and Waddington Landscape via Energy Indicator DOI Creative Commons
Hanshuang Li, Chunshen Long, Hong Yan

et al.

Research, Journal Year: 2023, Volume and Issue: 6

Published: Jan. 1, 2023

The precise characterization of cellular differentiation potency remains an open question, which is fundamentally important for deciphering the dynamics mechanism related to cell fate transition. We quantitatively evaluated different stem cells based on Hopfield neural network (HNN). results emphasized that can be approximated by energy values. then profiled Waddington landscape embryogenesis and reprogramming processes. at single-cell resolution further confirmed decision progressively specified in a continuous process. Moreover, transition from one steady state another processes was dynamically simulated ladder. These two metaphorized as motion descending ascending ladders, respectively. deciphered gene regulatory (GRN) driving Our study proposes new indicator characterize without prior knowledge, facilitating exploration potential plasticity.

Language: Английский

Citations

17
BMI1 enables interspecies chimerism with human pluripotent stem cells DOI Creative Commons
Ke Huang, Yanling Zhu, Yanlin Ma

et al.

Nature Communications, Journal Year: 2018, Volume and Issue: 9(1)

Published: Nov. 1, 2018

Human pluripotent stem cells (hPSCs) exhibit very limited contribution to interspecies chimeras. One explanation is that the conventional hPSCs are in a primed state and so unable form chimeras pre-implantation embryos. Here, we show undergo rapid apoptosis when injected into mouse While, forced-expression of BMI1, polycomb factor overcomes enables integrate embryos subsequently contribute with both embryonic extra-embryonic tissues. In addition, BMI1 also other species, such as rabbit pig. Notably, high expression anti-apoptosis indicators for naïve chimera Together, our findings reveal an initial barrier chimerism using provide rational improve it.

Language: Английский

Citations

49