Bone marrow stromal cell lines with lymphopoietic activity express high levels of a pre-B neoplasia-associated molecule

Whitlock, Cheryl A.; Tidmarsh, George F.; Müller‐Sieburg, Christa E.; Weissman, Irving L.

doi:10.1016/0092-8674(87)90709-4

Cited by 239 publications

(122 citation statements)

References 32 publications

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“…On day 21, cells were harvested and analyzed by flow cytometry. For neuronal induction, cells were placed on AC11 stromal cells (26) and cultured in Iscove's modified Dulbecco medium supplemented with 2 mM GlutaMax-1͞0.1 mM 2-mercaptoethanol͞0.1 M dexamethasone (Sigma)͞15% FCS͞100 units/ml penicillin͞100 g/ml streptomycin, and cells were analyzed for neuronal markers after 2 weeks of culture. Immunocytochemistry.…”

Section: Methodsmentioning

confidence: 99%

Enforced Bcl-2 expression overrides serum and feeder cell requirements for mouse embryonic stem cell self-renewal

Yamane

Dylla

Muijtjens

et al. 2005

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

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Leukemia inhibitory factor (LIF) is required, but not sufficient, for pluripotent mouse embryonic stem (ES) cell expansion in vitro in the absence of serum or a feeder cell layer, suggesting that additional signals are provided by serum or feeders that are necessary to support self-renewal. Here we show that transgenic ES cell lines expressing Bcl-2, an antiapoptotic protein, continue to self-renew in serum-and feeder-free conditions when supplemented with LIF; even in the absence of bone morphogenic proteins. Bcl-2-expressing clones sustain the characteristics of undifferentiated, pluripotent ES cells during long-term culture, and maintain their potential to differentiate into mature cell types. These results suggest that LIF and Bcl-2 overexpression are sufficient to expand these mouse pluripotent stem cells in vitro.leukemia inhibitory factor ͉ antiapoptotic protein ͉ pluripotency S tem cells are defined as cells that, at the single-cell level, are capable of self-renewal and differentiation to specialized cell types (1). ES cells are pluripotent stem cells derived from the inner cell mass of blastocysts (2) and can self-renew indefinitely in vitro in the presence of leukemia inhibitory factor (LIF) and FBS or mouse feeder layer cells, resulting in daughter cells that maintain their potential for multilineage differentiation (3, 4). When ES cells are maintained in serum-and feeder-free conditions, the number of undifferentiated cells quickly reaches a plateau and begins to decline after only a couple of passages (5), and cells with a non-ES cell morphology quickly arise in culture (6) despite the presence of LIF. Thus, additional factors provided by serum or feeders appear to be required to fully support the self-renewal of mouse ES cells.Bone morphogenic proteins (BMPs) have been implicated as the factor contained in serum or provided by feeder layers that acts in concert with LIF to maintain undifferentiated mouse ES cells in vitro (7). It was recently suggested that BMPs can replace serum and feeder cell requirements in ES cell culture by activating the Smad pathway and inducing expression of the Id gene, a common target of Smad signaling (8) that appears to block differentiation by negatively regulating basic helix-loophelix proteins (5). Although the exact mechanism by which BMP promotes self-renewal of ES cells is not certain, recent work suggests that it might also inhibit the mitogen-activated protein kinase (MAPK) pathway independent of Smads (7). Importantly, inhibition of p38 MAPK facilitates derivation of ES cells from blastocysts lacking Alk-3 (BMPRIA) (7), and ES cells can be derived from blastocysts lacking Smad4 (the common partner of all Smads; ref. 9), supporting the hypothesis that BMP acts by means of different mechanisms depending on the presence or absence of serum and feeders.Considering the possibility that serum and feeder cells provide cell survival signals manifest as growth factors and cytokines (10) and that extrinsic survival signals are especially critical in low cell density co...

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Section: Methodsmentioning

confidence: 99%

Enforced Bcl-2 expression overrides serum and feeder cell requirements for mouse embryonic stem cell self-renewal

Yamane

Dylla

Muijtjens

et al. 2005

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

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“…Placed under the kidney capsule in large cell numbers, SSCs form bone and cartilage in a morphologically correct manner (124)(125)(126)(127), with a bone marrow cavity containing host-derived HSCs and blood vessels. Of the stromal cell subsets, at least one was in the Whitlock clones (121), and at least three of the stroma support HSCs and hematopoiesis (124-127). As we have published recently, it has only taken us about 28 years to rediscover a cell we had prospectively isolated (121).…”

Section: Wwwannualreviewsorg • How One Thing Led To Anothermentioning

confidence: 99%

“…Of the stromal cell subsets, at least one was in the Whitlock clones (121), and at least three of the stroma support HSCs and hematopoiesis (124-127). As we have published recently, it has only taken us about 28 years to rediscover a cell we had prospectively isolated (121).…”

Section: Wwwannualreviewsorg • How One Thing Led To Anothermentioning

confidence: 99%

How One Thing Led to Another

Weissman

2016

Annu. Rev. Immunol.

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I started research in high school, experimenting on immunological tolerance to transplantation antigens. This led to studies of the thymus as the site of maturation of T cells, which led to the discovery, isolation, and clinical transplantation of purified hematopoietic stem cells (HSCs). The induction of immune tolerance with HSCs has led to isolation of other tissue-specific stem cells for regenerative medicine. Our studies of circulating competing germline stem cells in colonial protochordates led us to document competing HSCs. In human acute myelogenous leukemia we showed that all preleukemic mutations occur in HSCs, and determined their order; the final mutations occur in a multipotent progenitor derived from the preleukemic HSC clone. With these, we discovered that CD47 is an upregulated gene in all human cancers and is a “don't eat me” signal; blocking it with antibodies leads to cancer cell phagocytosis. CD47 is the first known gene common to all cancers and is a target for cancer immunotherapy.

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“…To assess their potential to generate NGN3-expressing cells, coculture of these cells with MEFs or PA6 feeders gave inconsistent results. However, systematic testing led to the discovery that AC6 cells, a mouse bone marrow-derived stromal line used for in vitro culture of lineagecommitted blood precursors (36), supported differentiation of ngn3-expressing cells from fraction I (Fig. 4).…”

Section: Isolation Of a Cd133 ؉ Cd49f High Ngn3 ؊ Pancreatic Compartmmentioning

confidence: 99%

Conserved markers of fetal pancreatic epithelium permit prospective isolation of islet progenitor cells by FACS

Sugiyama

Rodriguez

McLean

et al. 2007

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

143

142

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Prospective isolation and characterization of progenitor cells is a paradigmatic strategy for studies of organ development. However, extraction of viable cells, fractionation of lineages, and in vitro analysis of progenitors from the fetal pancreas in experimental organisms like mice has proved challenging and has not yet been reported for human fetal pancreas. Here, we report isolation of pancreatic islet progenitor cells from fetal mice by FACS. Monoclonal antibodies that recognize cell-surface proteins on candidate stem cells in brain, skin, and other organs enabled separation of major pancreatic cell lineages and isolation of native pancreatic cells expressing neurogenin 3, an established marker of islet progenitors. New in vitro cell culture methods permitted isolated mouse islet progenitors to develop into hormone-expressing endocrine cells. Insulin-producing cells derived in vitro required or expressed factors that regulate fetal ␤ cell differentiation; thus, the genetic programs normally controlling in vivo mouse islet development are similarly required in our system. Moreover, antibodies that recognize conserved orthologous cell-surface epitopes in human fetal pancreas allowed FACS-based enrichment of candidate islet progenitor cells expressing neurogenin 3. Our studies reveal previously undescribed strategies for prospective purification and analysis of pancreatic endocrine progenitor cells that should accelerate studies of islet development and replacement.diabetes ͉ pancreas ͉ stem/progenitor cell ͉ neurogenin 3 ͉ CD133

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Bone marrow stromal cell lines with lymphopoietic activity express high levels of a pre-B neoplasia-associated molecule

Cited by 239 publications

References 32 publications

Enforced Bcl-2 expression overrides serum and feeder cell requirements for mouse embryonic stem cell self-renewal

Enforced Bcl-2 expression overrides serum and feeder cell requirements for mouse embryonic stem cell self-renewal

How One Thing Led to Another

Conserved markers of fetal pancreatic epithelium permit prospective isolation of islet progenitor cells by FACS

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