Prion protein is expressed on long-term repopulating hematopoietic stem cells and is important for their self-renewal

Zhang, Cheng Cheng; Steele, Andrew D.; Lindquist, Susan; Lodish, Harvey F.

doi:10.1073/pnas.0510577103

Cited by 214 publications

(213 citation statements)

References 30 publications

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“…From these efforts a variety of physiological functions of PrP C have been suggested including: neural protection, 3 copper metabolism, 4 long-term memory formation, 5 and bone marrow renewal. 6 There is equal uncertainty of the mechanism of PrP Sc pathology.…”

Section: Resultsmentioning

confidence: 99%

Induction of ligand-specific PrP^Csignaling in human neuronal cells

Arsenault

Potter

et al. 2012

Prion

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Section: Resultsmentioning

confidence: 99%

Induction of ligand-specific PrP^Csignaling in human neuronal cells

Arsenault

Potter

et al. 2012

Prion

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“…1,2,11,31 Its physiological role is still described as a black box, enigmatic and obscure. 6,32 To our knowledge, there are only two reports describing the expression of PrP C Figure 3 PrP C inclusions are cytosolic and do not display characteristics of an aggresome.…”

Section: Discussionmentioning

confidence: 99%

Pronounced cytosolic aggregation of cellular prion protein in pancreatic β-cells in response to hyperglycemia

Strom¹,

Wang²,

Reimer

et al. 2007

Laboratory Investigation

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Cellular prion protein (PrP C ), an N-linked glycoprotein, is expressed in a variety of tissues, but its functions remain unclear. PrP C is abundantly expressed in the endocrine pancreas, which regulates blood glucose homeostasis. Therefore, we investigated whether the expression of PrP C was altered in islets of Langerhans in a model of spontaneous type 1 diabetes, the diabetes-prone BioBreeding (BBdp) rat and a model of b-cell adaptation to hyperglycemia, the chronic glucose-infused Sprague Dawley rat. Pancreatic sections from animals aged 7-100 days were stained immunohistochemically and evaluated using light, fluorescence and confocal microscopy. PrP C was ubiquitously expressed in all four major endocrine cell types within islets. Surprisingly, cytosolic inclusions containing PrP C were identified exclusively in a subpopulation of insulin-producing b-cells. The inclusions exhibited different molecular characteristics from the PrP aggregates previously described in vitro in neurons. The frequency of b-cells with PrP C inclusions increased with age and was threefold greater in diabetes-prone rats than in controls at 100 days. Cytosolic PrP C expression in b-cells was suppressed whereas the number and size of PrP C inclusions markedly increased in response to hyperglycemia during the first 2 days of continuous glucose infusion in Sprague Dawley rats. In summary, this is the first report describing in vivo cytosolic PrP C aggregation. These unique PrP C inclusions were b-cell specific, more frequent in diabetes-prone animals, and responded to hyperglycemia in glucose-infused Sprague Dawley rats. These data suggest a potential dysfunction in b-cells of diabetes-prone rats, and point to new avenues for the study of diabetes pathogenesis.

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“…For example, PrP c expression in vitro leads to lymphoid cell proliferation (Cashman et al, 1990;Li et al, 2001) or promotes human hematopoietic cell renewal (Zhang et al, 2006). In addition, PrP c is directly involved in tumor cell progression in several tissues.…”

Section: Prp C Cell Cycle Regulation and Differentiation: Jumping Tmentioning

confidence: 99%

New insights into cellular prion protein (PrPc) functions: The “ying and yang” of a relevant protein

Nicolas

Gavı́n

Rı́o

2009

Brain Research Reviews

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Prion protein is expressed on long-term repopulating hematopoietic stem cells and is important for their self-renewal

Cited by 214 publications

References 30 publications

Induction of ligand-specific PrP^Csignaling in human neuronal cells

Induction of ligand-specific PrP^Csignaling in human neuronal cells

Pronounced cytosolic aggregation of cellular prion protein in pancreatic β-cells in response to hyperglycemia

New insights into cellular prion protein (PrPc) functions: The “ying and yang” of a relevant protein

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Prion protein is expressed on long-term repopulating hematopoietic stem cells and is important for their self-renewal

Cited by 214 publications

References 30 publications

Induction of ligand-specific PrPCsignaling in human neuronal cells

Induction of ligand-specific PrPCsignaling in human neuronal cells

Pronounced cytosolic aggregation of cellular prion protein in pancreatic β-cells in response to hyperglycemia

New insights into cellular prion protein (PrPc) functions: The “ying and yang” of a relevant protein

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Product

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Induction of ligand-specific PrP^Csignaling in human neuronal cells

Induction of ligand-specific PrP^Csignaling in human neuronal cells