The Notch Pathway: Modulation of Cell Fate Decisions in Hematopoiesis

Ohishi, Kohshi; Varnum‐Finney, Barbara; Bernstein, Irwin D.

doi:10.1007/bf02982106

Cited by 51 publications

(44 citation statements)

References 176 publications

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“…The cell fate decision-related cell-surface receptors Notch1 and Notch2 are involved in hematopoietic lineage specification (31,32), but they are not targeted by Gfi-1 in myeloid cells.…”

Section: Resultsmentioning

confidence: 99%

Targets of the transcriptional repressor oncoprotein Gfi-1

Duan

Horwitz

2003

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

103

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The undersigned authors note the following: "We wish to bring to your attention an issue regarding our PNAS publication referenced above. Although we cite our earlier PNAS publication (see ref. Figs. 2 and 3 display the UWHBs for Hb β-subunit (pdb.1bz0, chain B) and human cellular prion protein (pdb.1qm0) (12)(13)(14). Within the natural interactive context of the Hb subunit, the UWHBs signal crucial binding regions (24): UWHBs (90, 94), (90, 95) are associated with the β-FG corner involved in the quaternary α1β2 interface; UWHB (5, 9) is adjacent to Glu-6 which in sickle cell anemia mutates to Val-6 and is located at the Val-6-(Phe-85, Leu-88) interface in the deoxyHbS fiber."The following text in the section titled 'Toward a Structural Diagnosis' on page 6449 of our text is similar to the text beginning in the last paragraph on page 2392 in ref. 23:The distribution of proteins according to their average extent of hydrogen bond wrapping and their spatial concentration of structural defects is shown in Fig. 5 (see also ref. 23). The sample of 2,811 PDB proteins is large enough to define a reliable abundance distribution with an inflection point at ρ = 6.20. The integration of the distribution over a ρ-interval gives the fraction of proteins whose ρ lies within that range. Of the 2,811 proteins examined, 2,572 have ρ > 6.20, and none of them is known to yield amyloid aggregation under physiological conditions entailing partial retention of structure. Strikingly, relatively few disease-related amyloidogenic proteins are known in the sparsely populated, underwrapped 3.5 < ρ < 6.20 range, with the cellular prion proteins located at the extreme of the spectrum (3.53 < ρ < 3.72)....The range of H-bond wrapping 3.5 < ρ < 4.6 of 20 sampled PDB membrane proteins has been included in Fig. 5 for comparison. As expected, such proteins do not have the stringent H-bond packing requirements of soluble proteins for their H bonds at the lipid interface. Thus, this comparison becomes suggestive in terms of elucidating the driving factor for aggregation in soluble proteins: Although the UWHB constitutes a structural defect in a soluble protein because of its vulnerability to water attack, it is not a structural defect in a membrane protein. The exposure of the polar amide and carbonyl of the unbound state to a nonpolar phase is thermodynamically unfavorable (22). The virtually identical ρ value for human prion and outer-membrane protein A (Fig. 5) is revealing in this regard.Furthermore, all known amyloidogenic proteins that occur naturally in complexed form have sufficient H-bond wrapping within their respective complexes (ρ value near 6.2). Their amyloidogenic propensity appears only under conditions in which the protein is dissociated from the complex (compare Fig. 5). This finding is corroborated by the following computation. If an intramolecular hydrogen bond is underwrapped within the isolated protein molecule but located at an interface upon complexation, then to determine its extent of wrapping within the complex, we take ...

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“…The cell fate decision-related cell-surface receptors Notch1 and Notch2 are involved in hematopoietic lineage specification (31,32), but they are not targeted by Gfi-1 in myeloid cells.…”

Section: Resultsmentioning

confidence: 99%

Targets of the transcriptional repressor oncoprotein Gfi-1

Duan

Horwitz

2003

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

103

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“…Hitherto, Notch has been considered a key developmental gene that coordinates a variety of transcriptional events to regulate somitogenesis and stem cell fate (30)(31)(32)(33)(34)(35)(36). In the skeletal context, studies have focused primarily on bone development in both mice and people.…”

Section: Discussionmentioning

confidence: 99%

Anabolic actions of Notch on mature bone

Liu

Ping

et al. 2016

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

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Notch controls skeletogenesis, but its role in the remodeling of adult bone remains conflicting. In mature mice, the skeleton can become osteopenic or osteosclerotic depending on the time point at which Notch is activated or inactivated. Using adult EGFP reporter mice, we find that Notch expression is localized to osteocytes embedded within bone matrix. Conditional activation of Notch signaling in osteocytes triggers profound bone formation, mainly due to increased mineralization, which rescues both age-associated and ovariectomy-induced bone loss and promotes bone healing following osteotomy. In parallel, mice rendered haploinsufficient in γ-secretase presenilin-1 (Psen1), which inhibits downstream Notch activation, display almost-absent terminal osteoblast differentiation. Consistent with this finding, pharmacologic or genetic disruption of Notch or its ligand Jagged1 inhibits mineralization. We suggest that stimulation of Notch signaling in osteocytes initiates a profound, therapeutically relevant, anabolic response.

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“…For example, the Notch-mediated process of lateral inhibition selects a single cell within a group of equivalent cells to adopt another cell fate than the remaining cells of that group. 40,41 As Notch is required to maintain primitive hematopoietic cells in an undifferentiated state, 42 it might be possible that 1 of the daughter cells activates the Notch signaling pathway in a process of lateral inhibition in its sister cell, resulting in the maintenance of the primitive cell fate in only 1 of the 2 cells.…”

Section: Discussionmentioning

confidence: 99%

Primitive human hematopoietic cells give rise to differentially specified daughter cells upon their initial cell division

Giebel

Zhang

Beckmann

et al. 2006

Blood

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It is often predicted that stem cells divide asymmetrically, creating a daughter cell that maintains the stem-cell capacity, and 1 daughter cell committed to differentiation. While asymmetric stem-cell divisions have been proven to occur in model organisms (eg, in Drosophila), it remains illusive whether primitive hematopoietic cells in mammals actually can divide asymmetrically. In our experiments we have challenged this question and analyzed the developmental capacity of separated offspring of primitive human hematopoietic cells at a single-cell level. We show for the first time that the vast majority of the most primitive, in vitro-detectable human hematopoietic cells give rise to daughter cells adopting different cell fates; 1 inheriting the developmental capacity of the mother cell, and 1 becoming more specified. In contrast, approximately half of the committed progenitor cells studied gave rise to daughter cells, both of which adopted the cell fate of their mother. Although our data are compatible with the model of asymmetric cell division, other mechanisms of cell fate specification are discussed. In addition, we describe a novel human hematopoietic progenitor cell that has the capacity to form natural killer (

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The Notch Pathway: Modulation of Cell Fate Decisions in Hematopoiesis

Cited by 51 publications

References 176 publications

Targets of the transcriptional repressor oncoprotein Gfi-1

Targets of the transcriptional repressor oncoprotein Gfi-1

Anabolic actions of Notch on mature bone

Primitive human hematopoietic cells give rise to differentially specified daughter cells upon their initial cell division

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