Abstract：
:Hematopoietic stem cells (HSCs) exist in a dormant state and progressively lose regenerative potency as they undergo successive divisions. Why this functional decline occurs and how this information is encoded is unclear. To better understand how this information is stored, we performed RNA sequencing on HSC populations differing only in their divisional history. Comparative analysis revealed that genes upregulated with divisions are enriched for lineage genes and regulated by cell-cycle-associated transcription factors, suggesting that proliferation itself drives lineage priming. Downregulated genes are, however, associated with an HSC signature and targeted by the Polycomb Repressive Complex 2 (PRC2). The PRC2 catalytic subunits Ezh1 and Ezh2 promote and suppress the HSC state, respectively, and successive divisions cause a switch from Ezh1 to Ezh2 dominance. We propose that cell divisions drive lineage priming and Ezh2 accumulation, which represses HSC signature genes to consolidate information on divisional history into memory.
journal_name
Stem Cell Reportsjournal_title
Stem cell reportsauthors
Bernitz JM,Rapp K,Daniel MG,Shcherbinin D,Yuan Y,Gomes A,Waghray A,Brosh R,Lachmann A,Ma'ayan A,Papatsenko D,Moore KAdoi
10.1016/j.stemcr.2020.03.005subject
Has Abstractpub_date
2020-04-14 00:00:00pages
561-574issue
4issn
2213-6711pii
S2213-6711(20)30095-3journal_volume
14pub_type
杂志文章abstract：:The core pluripotency transcription factor NANOG is critical for embryonic stem cell (ESC) self-renewal and somatic cell reprogramming. Although NANOG is phosphorylated at multiple residues, the role of NANOG phosphorylation in ESC self-renewal is incompletely understood, and no information exists regarding its functi...
journal_title：Stem cell reports
pub_type： 杂志文章
doi：10.1016/j.stemcr.2017.03.023
更新日期：2017-05-09 00:00:00
abstract：:Ischemic stroke enhances the proliferation of adult-generated precursor cells that ectopically migrate toward the infarct. Studies have correlated precursor cell proliferation and subsequent adult neurogenesis with enhanced stroke recovery, yet it remains unclear whether stroke can generate new neurons capable of func...
journal_title：Stem cell reports
pub_type： 杂志文章
doi：10.1016/j.stemcr.2018.10.011
更新日期：2018-12-11 00:00:00
abstract：:Spermatogonial stem cells (SSCs) serve as a resource for producing genetically modified animals. However, genetic manipulation of SSCs has met with limited success. Here, we show efficient gene transfer into SSCs via a lentivirus (FV-LV) using a fusion protein (F), a Sendai virus (SV) envelope protein involved in viri...
journal_title：Stem cell reports
pub_type： 杂志文章
doi：10.1016/j.stemcr.2020.02.001
更新日期：2020-03-10 00:00:00
abstract：:Human pluripotent stem cells are a valuable resource for transplantation, yet our ability to profile xenografts is largely limited to low-throughput immunohistochemical analysis by difficulties in readily isolating grafts for transcriptomic and/or proteomic profiling. Here, we present a simple methodology utilizing di...
journal_title：Stem cell reports
pub_type： 杂志文章
doi：10.1016/j.stemcr.2019.10.001
更新日期：2019-11-12 00:00:00
abstract：:Deletion of caudal/cdx genes alters hox gene expression and causes defects in posterior tissues and hematopoiesis. Yet, the defects in hox gene expression only partially explain these phenotypes. To gain deeper insight into Cdx4 function, we performed chromatin immunoprecipitation sequencing (ChIP-seq) combined with g...
journal_title：Stem cell reports
pub_type： 杂志文章
doi：10.1016/j.stemcr.2013.10.001
更新日期：2013-11-07 00:00:00
abstract：:The balance of self-renewal and differentiation in long-term repopulating hematopoietic stem cells (LT-HSC) must be strictly controlled to maintain blood homeostasis and to prevent leukemogenesis. Hematopoietic cytokines can induce differentiation in LT-HSCs; however, the molecular mechanism orchestrating this delicat...
journal_title：Stem cell reports
pub_type： 杂志文章
doi：10.1016/j.stemcr.2014.05.010
更新日期：2014-06-19 00:00:00
abstract：:Microglia, the immune cells of the brain, are crucial to proper development and maintenance of the CNS, and their involvement in numerous neurological disorders is increasingly being recognized. To improve our understanding of human microglial biology, we devised a chemically defined protocol to generate human microgl...
journal_title：Stem cell reports
pub_type： 杂志文章
doi：10.1016/j.stemcr.2017.04.023
更新日期：2017-06-06 00:00:00
abstract：:Pig embryonic stem cells (pESCs) have been considered an important candidate for preclinical research on human therapies. However, the lack of understanding of pig pluripotent networks has hampered establishment of authentic pESCs. Here, we report that FGF2, ACTVIN, and WNT signaling are essential to sustain pig pluri...
journal_title：Stem cell reports
pub_type： 杂志文章
doi：10.1016/j.stemcr.2019.05.028
更新日期：2019-07-09 00:00:00
abstract：:A large number of point mutations have been identified in induced pluripotent stem cell (iPSC) genomes to date. Whether these mutations are associated with iPSC generation is an important and controversial issue. In this study, we approached this critical issue in different ways, including an assessment of iPSCs versu...
journal_title：Stem cell reports
pub_type： 杂志文章
doi：10.1016/j.stemcr.2013.11.006
更新日期：2014-01-02 00:00:00
abstract：:Cell transplantation into immunodeficient recipients is a widely used approach to study stem cell and cancer biology; however, studying cell states post transplantation in vivo is inconvenient in mammals. Here, we generated a foxn1/Casper mutant zebrafish that is transparent and exhibits T cell deficiency. By employin...
journal_title：Stem cell reports
pub_type： 杂志文章
doi：10.1016/j.stemcr.2020.07.020
更新日期：2020-09-08 00:00:00
abstract：:Robust production of terminally differentiated cells from self-renewing resident stem cells is essential to maintain proper tissue architecture and physiological functions, especially in high-turnover tissues. However, the transcriptional networks that precisely regulate cell transition and differentiation are poorly ...
journal_title：Stem cell reports
pub_type： 杂志文章
doi：10.1016/j.stemcr.2020.01.003
更新日期：2020-02-11 00:00:00
abstract：:Human embryonic stem cells (hESCs) provide a platform for studying human development and understanding mechanisms underlying diseases. Retinoblastoma-1 (RB1) is a key regulator of cell cycling, of which biallelic inactivation initiates retinoblastoma, the most common congenital intraocular malignancy. We developed a m...
journal_title：Stem cell reports
pub_type： 杂志文章
doi：10.1016/j.stemcr.2017.03.005
更新日期：2017-05-09 00:00:00
abstract：:Heterozygous de novo mutations in GATA6 are the most frequent cause of pancreatic agenesis in humans. In mice, however, a similar phenotype requires the biallelic loss of Gata6 and its paralog Gata4. To elaborate the human-specific requirements for GATA6, we chose to model GATA6 loss in vitro by combining both gene-ed...
journal_title：Stem cell reports
pub_type： 杂志文章
doi：10.1016/j.stemcr.2018.12.003
更新日期：2019-01-08 00:00:00
abstract：:In various vertebrate species, the dorsal aorta (Ao) is the site of specification of adult hematopoietic stem cells (HSCs). It has been observed that the upregulation of essential hematopoietic transcription factors and the formation of specific intra-aortic hematopoietic cell clusters occur predominantly in the ventr...
journal_title：Stem cell reports
pub_type： 杂志文章
doi：10.1016/j.stemcr.2014.02.004
更新日期：2014-03-27 00:00:00
abstract：:Human stem cell-derived models of development and neurodegenerative diseases are challenged by cellular immaturity in vitro. Microengineered organ-on-chip (or Organ-Chip) systems are designed to emulate microvolume cytoarchitecture and enable co-culture of distinct cell types. Brain microvascular endothelial cells (BM...
journal_title：Stem cell reports
pub_type： 杂志文章
doi：10.1016/j.stemcr.2018.02.012
更新日期：2018-04-10 00:00:00
abstract：:Meiosis is the key step in gametogenesis. However, the mechanism of mammalian meiosis remains poorly understood due to the lack of an in vitro model. Here, we report that retinoic acid (RA) is sufficient for inducing leptotene/zygotene spermatocytes from cultured mouse spermatogonial stem cells. Multiple genes regulat...
journal_title：Stem cell reports
pub_type： 杂志文章
doi：10.1016/j.stemcr.2016.05.013
更新日期：2016-07-12 00:00:00
abstract：:ADP-ribosylation factor-like 4aa (Arl4aa) is a member of the ADP-ribosylation factor family. It is expressed in hematopoietic tissue during embryonic development, but its function was unknown. Zebrafish arl4aa is preferentially expressed in the ventral wall of the dorsal aorta (VDA) at 24 and 36 hpf and in caudal hema...
journal_title：Stem cell reports
pub_type： 杂志文章
doi：10.1016/j.stemcr.2020.02.012
更新日期：2020-04-14 00:00:00
abstract：:Structural phenotyping based on classical image feature detection has been adopted to elucidate the molecular mechanisms behind genetically or pharmacologically induced changes in cell morphology. Here, we developed a set of 11 metrics to capture the increasing sarcomere organization that occurs intracellularly during...
journal_title：Stem cell reports
pub_type： 杂志文章
doi：10.1016/j.stemcr.2015.01.020
更新日期：2015-03-10 00:00:00
abstract：:Cell division is a process by which a mother cell divides into genetically identical sister cells, although sister cells often display considerable diversity. In this report, over 350 sister embryonic stem cells (ESCs) were isolated through a microdissection method, and then expression levels of 48 key genes were exam...
journal_title：Stem cell reports
pub_type： 杂志文章
doi：10.1016/j.stemcr.2013.08.005
更新日期：2013-09-26 00:00:00
abstract：:Although pluripotent stem cells can generate various types of differentiated cells, it is unclear why lineage-committed stem/progenitor cells derived from pluripotent stem cells are decelerated and why the differentiation-resistant propensity of embryonic stem cell (ESC)/induced pluripotent stem cell (iPSC)-derived ce...
journal_title：Stem cell reports
pub_type： 杂志文章
doi：10.1016/j.stemcr.2018.12.018
更新日期：2019-02-12 00:00:00
abstract：:The microenvironment is a critical mediator of stem cell survival, proliferation, migration, and differentiation. The majority of preclinical studies involving transplantation of neural stem cells (NSCs) into the CNS have focused on injured or degenerating microenvironments, leaving a dearth of information as to how N...
journal_title：Stem cell reports
pub_type： 杂志文章
doi：10.1016/j.stemcr.2014.03.005
更新日期：2014-04-18 00:00:00
abstract：:Mesenchymal stem cells (MSCs) can donate mitochondria and rescue anthracycline-induced cardiomyocyte (CM) damage, although the underlying mechanisms remain elusive. We determined that the superior efficiency of mitochondrial transfer by human induced-pluripotent-stem-cell-derived MSCs (iPSC-MSCs) compared with bone ma...
journal_title：Stem cell reports
pub_type： 杂志文章
doi：10.1016/j.stemcr.2016.08.009
更新日期：2016-10-11 00:00:00
abstract：:The environment surrounding stem cells has the ability to elicit profound, heritable epigenetic changes orchestrated by multiple epigenetic mechanisms, which can be modulated by the level of specific metabolites. In this review, we highlight the significance of metabolism in regulating stem cell homeostasis, cell stat...
journal_title：Stem cell reports
pub_type： 杂志文章,评审
doi：10.1016/j.stemcr.2019.09.003
更新日期：2019-10-08 00:00:00
abstract：:Tight regulation of the balance between self-renewal and differentiation of neural stem cells is crucial to assure proper neural development. In this context, Notch signaling is a well-known promoter of stemness. In contrast, the bifunctional brain-enriched microRNA miR-9/9(∗) has been implicated in promoting neuronal...
journal_title：Stem cell reports
pub_type： 杂志文章
doi：10.1016/j.stemcr.2016.06.008
更新日期：2016-08-09 00:00:00
abstract：:The hematopoietic marrow microenvironment is composed of multiple cell types embedded in an extracellular matrix (ECM). We have explored marrow ECM using mass spectrometry and found dermatopontin (DPT), a small non-collagenous ECM protein, to be present. We found that DPT cooperates with other ECM proteins to promote ...
journal_title：Stem cell reports
pub_type： 杂志文章
doi：10.1016/j.stemcr.2017.07.021
更新日期：2017-09-12 00:00:00
abstract：:Differentiation of human embryonic stem cells into pancreatic β cells holds great promise for the treatment of diabetes. Recent advances have led to the production of glucose-responsive insulin-secreting cells in vitro, but resulting cells remain less mature than their adult primary β cell counterparts. The barrier(s)...
journal_title：Stem cell reports
pub_type： 杂志文章
doi：10.1016/j.stemcr.2019.11.009
更新日期：2020-01-14 00:00:00
abstract：:Pelizaeus-Merzbacher disease (PMD) is a fatal X-linked disorder caused by loss of myelinating oligodendrocytes and consequent hypomyelination. The underlying cellular and molecular dysfunctions are not fully defined, but therapeutic enhancement of oligodendrocyte survival could restore functional myelination in patien...
journal_title：Stem cell reports
pub_type： 杂志文章
doi：10.1016/j.stemcr.2018.07.015
更新日期：2018-09-11 00:00:00
abstract：:Mutations in the NADPH oxidase, which is crucial for the respiratory burst in phagocytes, result in chronic granulomatous disease (CGD). The only curative treatment option for CGD patients, who suffer from severe infections, is allogeneic bone marrow transplantation. Over 90% of patients with mutations in the p47phox ...
journal_title：Stem cell reports
pub_type： 杂志文章
doi：10.1016/j.stemcr.2019.08.008
更新日期：2019-10-08 00:00:00
abstract：:The ability to form teratomas in vivo containing multiple somatic cell types is regarded as functional evidence of pluripotency for human pluripotent stem cells (hPSCs). Since the Teratoma assay is animal dependent, laborious, and only qualitative, the PluriTest and the hPSC ScoreCard assay have been developed as in v...
journal_title：Stem cell reports
pub_type： 杂志文章
doi：10.1016/j.stemcr.2017.03.009
更新日期：2017-05-09 00:00:00
abstract：:Neurons differentiated from induced pluripotent stem cells (iPSCs) typically show regular spiking and synaptic activity but lack more complex network activity critical for brain development, such as periodic depolarizations including simultaneous involvement of glutamatergic and GABAergic neurotransmission. We generat...
journal_title：Stem cell reports
pub_type： 杂志文章
doi：10.1016/j.stemcr.2020.05.015
更新日期：2020-07-14 00:00:00
