Derivation of trophoblast stem cells from naïve human pluripotent stem cells

Dong, Chen; Beltcheva, Mariana; Gontarz, Paul; Zhang, Bo; Popli, Pooja; Fischer, Laura A.; Khan, Shafqat Ali; Park, Kyoung Mi; Yoon, Eun‐Ja; Xing, Xiaoyun; Kommagani, Ramakrishna; Wang, Ting; Solnica‐Krezel, Lilianna; Theunissen, Thorold W.

doi:10.7554/elife.52504

Cited by 225 publications

(336 citation statements)

References 69 publications

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“…Several reports also used TGF‐β/Activin A to establish naïve pluripotency in hPSCs (Qin et al , ). Consistent with this, it has been reported that inhibition of TGF‐β signaling in bona fide naïve pluripotent cells can generate extraembryonic trophectoderm indicating the dependency of human naïve pluripotency to TGF‐β signaling (Dong et al , ; preprint: Guo et al , ). Compared to primed hPSCs in which continuous supplementation of TGF‐β/Activin A is necessary to protect pluripotency, we found that transient stimulation of TGF‐β signaling is sufficient to induce and maintain the naïve‐like state in hPSCs.…”

Section: Discussionsupporting

confidence: 58%

Temporal activation of LRH‐1 and RAR‐γ in human pluripotent stem cells induces a functional naïve‐like state

et al. 2020

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Naïve pluripotency can be established in human pluripotent stem cells (hPSCs) by manipulation of transcription factors, signaling pathways, or a combination thereof. However, differences exist in the molecular and functional properties of naïve hPSCs generated by different protocols, which include varying similarities with pre-implantation human embryos, differentiation potential, and maintenance of genomic integrity. We show here that short treatment with two chemical agonists (2a) of nuclear receptors, liver receptor homologue-1 (LRH-1) and retinoic acid receptor gamma (RAR-c), along with 2i/LIF (2a2iL) induces naïve-like pluripotency in human cells during reprogramming of fibroblasts, conversion of pre-established hPSCs, and generation of new cell lines from blastocysts. 2a2iL-hPSCs match several defined criteria of naïve-like pluripotency and contribute to human-mouse interspecies chimeras. Activation of TGF-b signaling is instrumental for acquisition of naïvelike pluripotency by the 2a2iL induction procedure, and transient activation of TGF-b signaling substitutes for 2a to generate naïve-like hPSCs. We reason that 2a2iL-hPSCs are an easily attainable system to evaluate properties of naïve-like hPSCs and for various applications.

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Section: Discussionsupporting

confidence: 58%

Temporal activation of LRH‐1 and RAR‐γ in human pluripotent stem cells induces a functional naïve‐like state

et al. 2020

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“…As an alternative, and to test whether increased levels of ECAD could lead to trophoblast differentiation and cell cycle arrest, we decided to use human TSCs 33 as a model system. Importantly, human TSCs show transcriptional similarity to early post-implantation cytotrophoblast 34 . In parallel, we used human ESC cultures to model the post-implantation epiblast 35 .…”

Section: (Supplementarymentioning

confidence: 99%

Developmental potential of aneuploid human embryos cultured beyond implantation

Shahbazi

Wang²,

Tao³

et al. 2020

Nat Commun

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Aneuploidy, the presence of an abnormal number of chromosomes, is a major cause of early pregnancy loss in humans. Yet, the developmental consequences of specific aneuploidies remain unexplored. Here, we determine the extent of post-implantation development of human embryos bearing common aneuploidies using a recently established culture platform. We show that while trisomy 15 and trisomy 21 embryos develop similarly to euploid embryos, monosomy 21 embryos exhibit high rates of developmental arrest, and trisomy 16 embryos display a hypo-proliferation of the trophoblast, the tissue that forms the placenta. Using human trophoblast stem cells, we show that this phenotype can be mechanistically ascribed to increased levels of the cell adhesion protein E-CADHERIN, which lead to premature differentiation and cell cycle arrest. We identify three cases of mosaicism in embryos diagnosed as full aneuploid by pre-implantation genetic testing. Our results present the first detailed analysis of post-implantation development of aneuploid human embryos.

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“…During the preparation and revision of this manuscript, other groups have reported conflicting evidence that the potential to generate trophoblast is either higher in ground state or in expanded potential stem cells (Cinkornpumin et al, 2020;Dong et al, 2020;Gao et al, 2019). Gao et al claimed that expanded potential hPSC (hEPSC), but not naive hPSC (cultured in 5iLAF), can generate TSC.…”

Section: Discussionmentioning

confidence: 99%

Generation of human induced trophoblast stem cells

Castel

Meistermann

Bretin

et al. 2020

Preprint

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SUMMARYHuman trophoblast stem cells (hTSC) derived from blastocysts and first-trimester cytotrophoblasts offer an unprecedented opportunity to study the human placenta. However, access to human embryos and first trimester placentas is limited thus preventing the establishment of hTSC from a variety of genetic backgrounds associated with placental disorders. In the present study, we show that hTSC can be generated from numerous genetic backgrounds using post-natal cells via two alternative methods: (I) somatic cell reprogramming of adult fibroblasts using the Yamanaka factors, and (II) cell fate conversion of naive and extended pluripotent stem cells. The resulted induced and converted hTSC (hiTSC/hcTSC) recapitulated hallmarks of hTSC including long-term self-renewal, expression of specific transcription factors, transcriptome-side signature, and the potential to differentiate into syncytiotrophoblast and extravillous trophoblast cells. We also clarified the developmental stage of hTSC and show that these cells resemble post-implantation NR2F2+ cytotrophoblasts (day 8-10). Altogether, hTSC lines of diverse genetics origins open the possibility to model both placental development and diseases in a dish.HighlightsReprogramming of human somatic cells to induced hTSC with OSKMConversion of naive and extended hPSC to hTSCGenetic diversity of hTSC linesDevelopmental matching of hTSC in the peri-implantation human embryo

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Derivation of trophoblast stem cells from naïve human pluripotent stem cells

Cited by 225 publications

References 69 publications

Temporal activation of LRH‐1 and RAR‐γ in human pluripotent stem cells induces a functional naïve‐like state

Temporal activation of LRH‐1 and RAR‐γ in human pluripotent stem cells induces a functional naïve‐like state

Developmental potential of aneuploid human embryos cultured beyond implantation

Generation of human induced trophoblast stem cells

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