Modeling Glioma Intratumoral Heterogeneity with Primary Human Neural Stem and Progenitor Cells.

Glioblastoma multiforme (GBM) is a deadly form of glioma notable for its significant intratumoral heterogeneity, which is believed to drive therapy resistance. GBM has been observed to mimic a neural stem cell hierarchy reminiscent of normal brain development. However, it is still unclear how cell-of-origin shapes intratumoral heterogeneity.

Purification and characterization of human neural stem and progenitor cells.

The human brain undergoes rapid development at mid-gestation from a pool of neural stem and progenitor cells (NSPCs) that give rise to the neurons, oligodendrocytes, and astrocytes of the mature brain. Functional study of these cell types has been hampered by a lack of precise purification methods. We describe a method for prospectively isolating ten distinct NSPC types from the developing human brain using cell-surface markers.

EpoR stimulates rapid cycling and larger red cells during mouse and human erythropoiesis.

The erythroid terminal differentiation program couples sequential cell divisions with progressive reductions in cell size. The erythropoietin receptor (EpoR) is essential for erythroblast survival, but its other functions are not well characterized. Here we use Epor mouse erythroblasts endowed with survival signaling to identify novel non-redundant EpoR functions.

Reprogramming progressive cells display low CAG promoter activity.

There is wide variability in the propensity of somatic cells to reprogram into pluripotency in response to the Yamanaka factors. How to segregate these variabilities to enrich for cells of specific traits that reprogram efficiently remains challenging. Here we report that the variability in reprogramming propensity is associated with the activity of the MKL1/SRF transcription factor and concurs with small cell size as well as rapid cell cycle.

Resolving Cell Cycle Speed in One Snapshot with a Live-Cell Fluorescent Reporter.

Cell proliferation changes concomitantly with fate transitions during reprogramming, differentiation, regeneration, and oncogenesis. Methods to resolve cell cycle length heterogeneity in real time are currently lacking. Here, we describe a genetically encoded fluorescent reporter that captures live-cell cycle speed using a single measurement.

The palette of techniques for cell cycle analysis.

The cell division cycle is the generational period of cellular growth and propagation. Cell cycle progression needs to be highly regulated to preserve genomic fidelity while increasing cell number. In multicellular organisms, the cell cycle must also coordinate with cell fate specification during development and tissue homeostasis.

YAP Non-cell-autonomously Promotes Pluripotency Induction in Mouse Cells.

Yes-associated protein (YAP) is known to promote the stemness of multiple stem cell types, including pluripotent stem cells, while also antagonizing pluripotency during early embryogenesis. How YAP accomplishes these distinct functions remains unclear. Here, we report that, depending on the specific cells in which it is expressed, YAP could exhibit opposing effects on pluripotency induction from mouse somatic cells.

Publisher Correction: MLL-AF9 initiates transformation from fast-proliferating myeloid progenitors.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

MLL-AF9 initiates transformation from fast-proliferating myeloid progenitors.

Cancer is a hyper-proliferative disease. Whether the proliferative state originates from the cell-of-origin or emerges later remains difficult to resolve. By tracking de novo transformation from normal hematopoietic progenitors expressing an acute myeloid leukemia (AML) oncogene MLL-AF9, we reveal that the cell cycle rate heterogeneity among granulocyte-macrophage progenitors (GMPs) determines their probability of transformation.

Cell cycle dynamics in the reprogramming of cellular identity.

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.

MKL1-actin pathway restricts chromatin accessibility and prevents mature pluripotency activation.

Actin cytoskeleton is well-known for providing structural/mechanical support, but whether and how it regulates chromatin and cell fate reprogramming is far less clear. Here, we report that MKL1, the key transcriptional co-activator of many actin cytoskeletal genes, regulates genomic accessibility and cell fate reprogramming. The MKL1-actin pathway weakens during somatic cell reprogramming by pluripotency transcription factors.