Proliferation and differentiation of mouse embryonic stem cells lacking all lamins

Kim, Young-Jo; Zheng, Xiaobin; Zheng, Yixian

doi:10.1038/cr.2013.118

Cited by 56 publications

(68 citation statements)

References 12 publications

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“…The fact that keratinocytes and fibroblasts were able to survive and proliferate in the absence of nuclear lamins was intriguing, given the reports claiming essential roles for nuclear lamins in the nucleus (1)(2)(3)(4)(5)(6)(7)(8). On the other hand, our findings were consistent with a recent study reporting that mouse embryonic stem (ES) cells proliferate normally in the absence of nuclear lamins (11). Interestingly, the nuclear lamin-deficient ES cells, when injected into nude mice, formed teratomas containing endodermal, mesodermal, and ectodermal structures.…”

Section: Discussionsupporting

confidence: 82%

“…In considering our findings, there is a formal possibility that the trace amounts of the truncated lamin A are sufficient to overcome a defect in DNA synthesis and mitosis and thereby allow keratinocytes to proliferate and differentiate. However, this possibility seems very remote, particularly given the ability of lamindeficient ES cells to proliferate and differentiate into teratomas (11). In the latter ES cell studies, the Lmna knockout was achieved with a gene-targeting strategy distinct from the one used by Sullivan and coworkers.…”

Section: Discussionmentioning

confidence: 99%

“…Similarly, hepatocyte-specific Lmnb1 Lmnb2 knockout mice had normal liver histology and normal liver function tests (10). These studies cast doubt on the notion that B-type lamins are essential for DNA replication and mitosis but did not exclude the possibility that these functions were simply subserved by lamins A and C. Recently, a paper in Cell Research (11) reported that mouse embryonic stem cells proliferate normally in the absence of all nuclear lamins. At face value, that paper refuted the idea that nuclear lamins are crucial for mitosis and DNA replication, at least in stem cells, but many questions remain.…”

mentioning

confidence: 97%

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An Absence of Nuclear Lamins in Keratinocytes Leads to Ichthyosis, Defective Epidermal Barrier Function, and Intrusion of Nuclear Membranes and Endoplasmic Reticulum into the Nuclear Chromatin

Jung

Tatar

et al. 2014

Molecular and Cellular Biology

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d B-type lamins (lamins B1 and B2) have been considered to be essential for many crucial functions in the cell nucleus (e.g., DNA replication and mitotic spindle formation). However, this view has been challenged by the observation that an absence of both B-type lamins in keratinocytes had no effect on cell proliferation or the development of skin and hair. The latter findings raised the possibility that the functions of B-type lamins are subserved by lamins A and C. To explore that idea, we created mice lacking all nuclear lamins in keratinocytes. Those mice developed ichthyosis and a skin barrier defect, which led to death from dehydration within a few days after birth. Microscopy of nuclear-lamin-deficient skin revealed hyperkeratosis and a disordered stratum corneum with an accumulation of neutral lipid droplets; however, BrdU incorporation into keratinocytes was normal. Skin grafting experiments confirmed the stratum corneum abnormalities and normal BrdU uptake. Interestingly, the absence of nuclear lamins in keratinocytes resulted in an interspersion of nuclear/endoplasmic reticulum membranes with the chromatin. Thus, a key function of the nuclear lamina is to serve as a "fence" and prevent the incursion of cytoplasmic organelles into the nuclear chromatin.T he B-type lamins, which are expressed in virtually all cells from the earliest stages of development, have been assumed to play vital functions in the cell nucleus (1-8). Multiple studies contributed to this view. One group found lamin B at sites of DNA replication during S-phase and suggested that it was important for DNA replication (1). Disruption of nuclear lamin organization with a dominant negative lamin B mutant in Xenopus egg extracts inhibited DNA replication (2, 3), mitotic spindle assembly (4), and nuclear envelope assembly in interphase (5). An RNA interference (RNAi) knockdown of lamin B1 and lamin B2 was reported to lead to mitotic arrest and apoptosis (6). Other studies reported that B-type lamins were important for chromatin organization and proper gene expression (7,8).The view that B-type lamins play crucial roles in the cell nucleus likely dampened enthusiasm for testing the importance of B-type lamins in knockout mice. Ultimately, however, Yang et al. (9) created conditional knockout alleles for both Lmnb1 and Lmnb2 and used those alleles to generate keratinocyte-specific Lmnb1 Lmnb2 knockout mice. Remarkably, a complete absence of both lamin B1 and lamin B2 in keratinocytes had no discernible effect on cell growth or the complex developmental programs involved in the formation of the epidermis, hair, and nails. By electron microscopy, the nuclear envelope and heterochromatin distribution appeared normal in Lmnb1 Lmnb2-deficient keratinocytes (9). Similarly, hepatocyte-specific Lmnb1 Lmnb2 knockout mice had normal liver histology and normal liver function tests (10). These studies cast doubt on the notion that B-type lamins are essential for DNA replication and mitosis but did not exclude the possibility that these functions were si...

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Section: Discussionsupporting

confidence: 82%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 97%

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An Absence of Nuclear Lamins in Keratinocytes Leads to Ichthyosis, Defective Epidermal Barrier Function, and Intrusion of Nuclear Membranes and Endoplasmic Reticulum into the Nuclear Chromatin

Jung

Tatar

et al. 2014

Molecular and Cellular Biology

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“…According to this interpretation, the absence of all nuclear lamins in Lmnb2/Lmnb1 doubleknockout neurons puts that cell type on an inexorable path to cell death. However, the interpretation may not be that simple, particularly in light of the studies by Kim et al, 16 which showed that mouse embryonic stem cells proliferate normally in the absence of all nuclear lamins.…”

Section: Crucial Roles For B-type Lamins In the Brainmentioning

confidence: 82%

“…However, that notion might be only partially correct. Kim et al 16 recently generated mouse embryonic stem cells lacking all nuclear lamins and found that they proliferated normally and formed large teratomas in mice. Those studies obviously undercut the idea that nuclear lamins play vital roles in DNA replication and mitosis but do not exclude roles for the nuclear lamina in maintaining nuclear structure.…”

Section: Do Lamin B1 and Lamin B2 Have Redundant Functions?mentioning

confidence: 99%

Do lamin B1 and lamin B2 have redundant functions?

Lee

Jung

Fong

et al. 2014

Nucleus

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Cell cycle dynamics in the reprogramming of cellular identity

Eastman

Guo

2019

FEBS Letters

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Reprogramming of cellular identity is fundamentally at odds with replication of the genome: cell fate reprogramming requires complex multidimensional epigenomic changes, whereas genome replication demands fidelity. In this review, we discuss how the pace of the genome's replication and cell cycle influences the way daughter cells take on their identity. We highlight several biochemical processes that are pertinent to cell fate control, whose propagation into the daughter cells should be governed by more complex mechanisms than simple templated replication. With this mindset, we summarize multiple scenarios where rapid cell cycle could interfere with cell fate copying and promote cell fate reprogramming. Prominent examples of cell fate regulation by specific cell cycle phases are also discussed. Overall, there is much to be learned regarding the relationship between cell fate reprogramming and cell cycle control. Harnessing cell cycle dynamics could greatly facilitate the derivation of desired cell types.

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Proliferation and differentiation of mouse embryonic stem cells lacking all lamins

Cited by 56 publications

References 12 publications

An Absence of Nuclear Lamins in Keratinocytes Leads to Ichthyosis, Defective Epidermal Barrier Function, and Intrusion of Nuclear Membranes and Endoplasmic Reticulum into the Nuclear Chromatin

An Absence of Nuclear Lamins in Keratinocytes Leads to Ichthyosis, Defective Epidermal Barrier Function, and Intrusion of Nuclear Membranes and Endoplasmic Reticulum into the Nuclear Chromatin

Do lamin B1 and lamin B2 have redundant functions?

Cell cycle dynamics in the reprogramming of cellular identity

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