Stem Cell Reviews and Reports

Ratajczak, Mariusz Z.

doi: 10.1007/s12015-022-10484-zpmid: 36527569

Roy, Ankan; Patra, Samir Kumar

doi: 10.1007/s12015-022-10448-3pmid: 35997871

Molecular views of plasma membrane organization and dynamics are gradually changing over the past fifty years. Dynamics of plasma membrane instigate several signaling nexuses in eukaryotic cells. The striking feature of plasma membrane dynamics is that, it is internally transfigured into various subdomains of clustered macromolecules. Lipid rafts are nanoscale subdomains, enriched with cholesterol and sphingolipids, reside as floating entity mostly on the exoplasmic leaflet of the lipid bilayer. In terms of functionality, lipid rafts are unique among other membrane subdomains. Herein, advances on the roles of lipid rafts in cellular physiology and homeostasis are discussed, precisely, on how rafts dynamically harbor signaling proteins, including GPCRs, catalytic receptors, and ionotropic receptors within it and orchestrate multiple signaling pathways. In the developmental proceedings signaling are designed for patterning of overall organism and they differ from the somatic cell physiology and signaling of fully developed organisms. Some of the developmental signals are characteristic in maintenance of stemness and activated during several types of tumor development and cancer progression. The harmony between extracellular signaling and lineage specific transcriptional programs are extremely important for embryonic development. The roles of plasma membrane lipid rafts mediated signaling in lineage specificity, early embryonic development, stem cell maintenance are emerging. In view of this, we have highlighted and analyzed the roles of lipid rafts in receptor organization, cell signaling, and gene expression during embryonic development; from pre-implantation through the post-implantation phase, in stem cell and cancer biology.Graphical Abstract[graphic not available: see fulltext]

Zafarani, Alireza; Taghavi-Farahabadi, Mahsa; Razizadeh, Mohammad Hossein; Amirzargar, Mohammad Reza; Mansouri, Mansoure; Mahmoudi, Mohammad

doi: 10.1007/s12015-022-10449-2pmid: 35994137

Natural killer (NK) cells are one of the innate immune cells that play an important role in preventing and controlling tumors and viral diseases, but their role in hematopoietic stem cell transplantation (HCT) is not yet fully understood. However, according to some research, these cells can prevent infections and tumor relapse without causing graft versus host disease (GVHD). In addition to NK cells, several studies are about the anti-leukemia effects of NK cell-derived exosomes that can highlight their roles in graft-versus-leukemia (GVL). In this paper, we intend to investigate the results of various articles on the role of NK cells in allogeneic hematopoietic cell transplantation and also their exosomes in GVL. Also, we have discussed the antiviral effects of these cells in post-HCT cytomegalovirus infection.Graphical Abstract[graphic not available: see fulltext]

Kong, Haiying; Liu, Peiqi; Li, Hongwen; Zeng, Xiantao; Xu, Peiwu; Yao, Xinhui; Liu, Senqing; Cheng, Chak Kwong; Xu, Jian

doi: 10.1007/s12015-022-10342-ypmid: 35132538

Dental mesenchymal stem cells (MSCs) are characterized by unlimited self-renewal ability and high multidirectional differentiation potential. Since dental MSCs can be easily isolated and exhibit a high capability to differentiate into odontogenic cells, they are considered as attractive therapeutic agents in regenerative dentistry. Recently, MSC-derived extracellular vesicles (MSC-EVs) have attracted widespread attention as carriers for cell-free therapy due to their potential functions. Many studies have shown that MSC-EVs can mediate microenvironment at tissue damage site, and coordinate the regeneration process. Additionally, MSC-EVs can mediate intercellular communication, thus affecting the phenotypes and functions of recipient cells. In this review, we mainly summarized the types of MSCs that could be potentially applied in regenerative dentistry, the possible molecular cargos of MSC-EVs, and the major effects of MSC-EVs on the therapeutic induction of osteogenic differentiation.Graphical abstract[graphic not available: see fulltext]

Herdenberg, Carl; Hedman, Håkan

doi: 10.1007/s12015-022-10442-9pmid: 35969315

Leucine-rich repeats and immunoglobulin-like domains (LRIG) proteins are evolutionarily conserved integral membrane proteins. Mammalian LRIG1 regulates stem cell quiescence in various tissue compartments, including compartments in the epidermis, oral mucosa, intestines, neural system, and incisors. The planarian LRIG1 homolog regulates the quiescence of multipotent neoblasts. The mechanism through which LRIG proteins regulate stem cell quiescence has not been well documented, although it is generally assumed that LRIG1 regulates the epidermal growth factor receptor (EGFR) or other receptor tyrosine kinases. However, Lrig-null (Lrig1-/-;Lrig2-/-; and Lrig3-/-) mouse embryonic fibroblasts (MEFs) have been recently found to exhibit apparently normal receptor tyrosine kinase functions. Moreover, bone morphogenetic protein (BMP) signaling has been shown to depend on LRIG1 and LRIG3 expression. BMPs are well-known regulators of stem cell quiescence. Here, we hypothesize that LRIG1 might regulate stem cell quiescence by promoting BMP signaling.Graphical abstractHYPOTHESIS: Based on recent findings, it is hypothesized that LRIG1 regulates stem cell quiescence in mammalian tissues as well as in planarian neoblasts by promoting BMP signaling.[graphic not available: see fulltext]

Eisa, Yusra A.; Guo, Ying; Yang, Feng-Chun

doi: 10.1007/s12015-022-10447-4pmid: 36008597

Epigenetic regulation of gene expression represents an important mechanism in the maintenance of stem cell function. Alterations in epigenetic regulation contribute to the pathogenesis of hematological malignancies. Plant homeodomain finger protein 6 (PHF6) is a member of the plant homeodomain (PHD)-like zinc finger family of proteins that is involved in transcriptional regulation through the modification of the chromatin state. Germline mutation of PHF6 is the causative genetic alteration of the X-linked mental retardation Borjeson–Forssman–Lehmann syndrome (BFLS). Somatic mutations in PHF6 are identified in human leukemia, such as adult T-cell acute lymphoblastic leukemia (T-ALL, ~ 38%), pediatric T-ALL (~ 16%), acute myeloid leukemia (AML, ~ 3%), chronic myeloid leukemia (CML, ~ 2.5%), mixed phenotype acute leukemia (MPAL, ~ 20%), and high-grade B-cell lymphoma (HGBCL, ~ 3%). More recent studies imply an oncogenic effect of PHF6 in B-cell acute lymphoblastic leukemia (B-ALL) and solid tumors. These data demonstrate that PHF6 could act as a double-edged sword, either a tumor suppressor or an oncogene, in a lineage-dependent manner. However, the underlying mechanisms of PHF6 in normal hematopoiesis and leukemogenesis remain largely unknown. In this review, we summarize current knowledge of PHF6, emphasizing the role of PHF6 in hematological malignancies.Graphical abstractEpigenetic regulation of PHF6 in B-ALL. PHF6 maintains a chromatin structure that is permissive to B-cell identity genes, but not T-cell-specific genes (left). Loss of PHF6 leads to aberrant expression of B-cell- and T-cell-specific genes resulting from lineage promiscuity and binding of T-cell transcription factors (right).[graphic not available: see fulltext]

Tooley, John G.; Catlin, James P.; Tooley, Christine E. Schaner

doi: 10.1007/s12015-022-10444-7pmid: 36094754

The methyltransferase-like (METTL) family is a diverse group of methyltransferases that can methylate nucleotides, proteins, and small molecules. Despite this diverse array of substrates, they all share a characteristic seven-beta-strand catalytic domain, and recent evidence suggests many also share an important role in stem cell biology. The most well characterized family members METTL3 and METTL14 dimerize to form an N6-methyladenosine (m6A) RNA methyltransferase with established roles in cancer progression. However, new mouse models indicate that METTL3/METTL14 are also important for embryonic stem cell (ESC) development and postnatal hematopoietic and neural stem cell self-renewal and differentiation. METTL1, METTL5, METTL6, METTL8, and METTL17 also have recently identified roles in ESC pluripotency and differentiation, while METTL11A/11B, METTL4, METTL7A, and METTL22 have been shown to play roles in neural, mesenchymal, bone, and hematopoietic stem cell development, respectively. Additionally, a variety of other METTL family members are translational regulators, a role that could place them as important players in the transition from stem cell quiescence to differentiation. Here we will summarize what is known about the role of METTL proteins in stem cell differentiation and highlight the connection between their growing importance in development and their established roles in oncogenesis.Graphical abstract[graphic not available: see fulltext]

Abdelbaset-Ismail, Ahmed; Ciechanowicz, Andrzej K.; Bujko, Kamila; Ratajczak, Janina; Kucia, Magdalena; Ratajczak, Mariusz Z.

doi: 10.1007/s12015-022-10481-2pmid: 36441489

Proliferation, metabolism, and migration of hematopoietic stem/progenitor cells (HSPCs) are coordinated by receptors expressed on outer cell membranes that are integrated into microdomains, known as membrane lipid rafts (MLRs). These structures float freely in the cell membrane bilayer and are enriched in cholesterol and sphingolipids for their functional integrity. Receptors, if expressed in MLRs, have prolonged occupancy on the cell surface and enhanced signaling power. Based on this, we have become interested in the regulation of synthesis of MLRs components in HSPCs. To address this, we tested the effect of selected factors that promote proliferation or migration and their potential involvement in the synthesis of MLRs components in HSPCs. Based on our previous research showing that HSPCs from Nox2-KO and Nlrp3-KO mice display a profound defect in MLRs formation, we focused on the role of Nox2-ROS-Nlrp3 inflammasome in regulating lipogenesis in HSPCs. We found that while at steady state conditions, Nox2-derived ROS is required for a proper expression of enzymes regulating lipogenesis, during inflammation, this effect is augmented by Nlrp3 inflammasome. Thus, our data sheds new light on the regulation of lipogenesis in HSPCs and the involvement of the Nox2-ROS-Nlrp3 inflammasome axis that differently regulates lipogenesis at steady state conditions and in response to inflammation, modulating MLRs-mediated responsiveness of these cells to external stimuli.Graphical Abstract[graphic not available: see fulltext]

Amel, Atoosa; Rossouw, Simoné; Goolam, Mubeen

doi: 10.1007/s12015-022-10462-5pmid: 36308705

By virtue of its inaccessible nature, mammalian implantation stage development has remained one of the most enigmatic and hard to investigate periods of embryogenesis. Derived from pluripotent stem cells, gastruloids recapitulate key aspects of gastrula-stage embryos and have emerged as a powerful in vitro tool to study the architectural features of early post-implantation embryos. While the majority of the work in this emerging field has focused on the use of gastruloids to model embryogenesis, their tractable nature and suitability for high-throughput scaling, has presented an unprecedented opportunity to investigate both developmental and environmental aberrations to the embryo as they occur in vitro. This review summarises the recent developments in the use of gastruloids to model congenital anomalies, their usage in teratogenicity testing, and the current limitations of this emerging field.

Mezine, Fariza; Guerin, Coralie L.; Philippe, Aurélien; Gendron, Nicolas; Soret, Lou; Sanchez, Olivier; Mirault, Tristan; Diehl, Jean-Luc; Chocron, Richard; Boulanger, Chantal M.; Smadja, David M.

doi: 10.1007/s12015-022-10446-5