Derivation Conditions Impact X-Inactivation Status in Female Human Induced Pluripotent Stem Cells

Tomoda, Kiichiro; Takahashi, Kazutoshi; Leung, Karen; Okada, Aki; Narita, Megumi; Yamada, N. Alice; Eilertson, Kirsten; Tsang, Peter; Baba, Shiro; White, Mark P.; Sami, Salma; Srivastava, Deepak; Conklin, Bruce R.; Panning, Barbara; Yamanaka, Shinya

doi:10.1016/j.stem.2012.05.019

Cited by 103 publications

(134 citation statements)

References 33 publications

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“…Previous and our current study clearly show that the human reprogramming process takes more time than we thought it would and the maturation step is important 29 . Although we have little evidence for the inevitability of the transition, this observation led us to find FOXH1 as an enhancer of reprogramming.…”

Section: Discussionsupporting

confidence: 58%

Induction of pluripotency in human somatic cells via a transient state resembling primitive streak-like mesendoderm

et al. 2014

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During mammalian embryonic development, the primitive streak initiates the differentiation of pluripotent epiblast cells into germ layers. Pluripotency can be reacquired in committed somatic cells using a combination of a handful of transcription factors, such as OCT3/4, SOX2, KLF4 and c-MYC (hereafter referred to as OSKM), albeit with low efficiency. Here we show that during OSKM-induced reprogramming towards pluripotency in human cells, intermediate cells transiently show gene expression profiles resembling mesendoderm, which is a major component of the primitive streak. Based on these findings, we discover that forkhead box H1 (FOXH1), a transcription factor required for anterior primitive streak specification during early development, significantly enhances the reprogramming efficiency of human fibroblasts by promoting their maturation, including mesenchymal to epithelial transition and the activation of late pluripotency markers. These results demonstrate that during the reprogramming process, human somatic cells go through a transient state that resembles mesendoderm.

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Section: Discussionsupporting

confidence: 58%

Induction of pluripotency in human somatic cells via a transient state resembling primitive streak-like mesendoderm

et al. 2014

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“…During somatic cell reprogramming, the human Xi is reliably reactivated in hiPSCs reprogrammed on SNL feeder cells (11), implicating the LIF signaling pathway in this transition. However, LIF alone is insufficient to mediate Xi reactivation, suggesting that the SNL feeder culture condition contains additional factors that mediate this epigenetic change.…”

Section: Resultsmentioning

confidence: 99%

“…We reported that culture conditions impact X chromosome inactivation (XCI) status in human induced pluripotent stem cells (hiPSCs) (11). hiPSC lines reprogrammed and maintained on LIFexpressing SNL feeder cells (12) are predominantly XaXa, whereas hiPSC lines derived on MEF feeder cells are mainly XaXi.…”

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confidence: 99%

Autotaxin-mediated lipid signaling intersects with LIF and BMP signaling to promote the naive pluripotency transcription factor program

Kime

Sakaki-Yumoto

Goodrich

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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Developmental signaling molecules are used for cell fate determination, and understanding how their combinatorial effects produce the variety of cell types in multicellular organisms is a key problem in biology. Here, we demonstrate that the combination of leukemia inhibitory factor (LIF), bone morphogenetic protein 4 (BMP4), lysophosphatidic acid (LPA), and ascorbic acid (AA) efficiently converts mouse primed pluripotent stem cells (PSCs) into naive PSCs. Signaling by the lipid LPA through its receptor LPAR1 and downstream effector Rho-associated protein kinase (ROCK) cooperated with LIF signaling to promote this conversion. BMP4, which also stimulates conversion to naive pluripotency, bypassed the need for exogenous LPA by increasing the activity of the extracellular LPA-producing enzyme autotaxin (ATX). We found that LIF and LPA-LPAR1 signaling affect the abundance of signal transducer and activator of transcription 3 (STAT3), which induces a previously unappreciated Kruppel-like factor (KLF)2-KLF4-PR domain 14 (PRDM14) transcription factor circuit key to establish naive pluripotency. AA also affects this transcription factor circuit by controlling PRDM14 expression. Thus, our study reveals that ATX-mediated autocrine lipid signaling promotes naive pluripotency by intersecting with LIF and BMP4 signaling.

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“…Conversely, Tomoda et al demonstrated that X-chromosome reactivation can occur in human iPSCs by extending the time of post-reprogramming culture and using SNL feeder cells that overexpress LIF (Tomoda et al, 2012). Thus, the Xi found during embryogenesis can be gradually reactivated over time by cell reprogramming (Fig.…”

Section: X-chromosome Activitymentioning

confidence: 99%

A developmental framework for induced pluripotency

Takahashi

Yamanaka

2015

Development

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During development, cells transition from a pluripotent to a differentiated state, generating all the different types of cells in the body. Development is generally considered an irreversible process, meaning that a differentiated cell is thought to be unable to return to the pluripotent state. However, it is now possible to reprogram mature cells to pluripotency. It is generally thought that reprogramming is accomplished by reversing the natural developmental differentiation process, suggesting that the two mechanisms are closely related. Therefore, a detailed study of cell reprogramming has the potential to shed light on unexplained developmental mechanisms and, conversely, a better understanding of developmental differentiation can help improve cell reprogramming. However, fundamental differences between reprogramming processes and multi-lineage specification during early embryonic development have also been uncovered. In addition, there are multiple routes by which differentiated cells can re-enter the pluripotent state. In this Review, we discuss the connections and disparities between differentiation and reprogramming, and assess the degree to which reprogramming can be considered as a simple reversal of development.

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Derivation Conditions Impact X-Inactivation Status in Female Human Induced Pluripotent Stem Cells

Cited by 103 publications

References 33 publications

Induction of pluripotency in human somatic cells via a transient state resembling primitive streak-like mesendoderm

Induction of pluripotency in human somatic cells via a transient state resembling primitive streak-like mesendoderm

Autotaxin-mediated lipid signaling intersects with LIF and BMP signaling to promote the naive pluripotency transcription factor program

A developmental framework for induced pluripotency

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