scholarly journals Intermediate progenitor cells provide a transition between hematopoietic progenitors and their differentiated descendants

Development ◽  
2021 ◽  
Vol 148 (24) ◽  
Author(s):  
Carrie M. Spratford ◽  
Lauren M. Goins ◽  
Fangtao Chi ◽  
Juliet R. Girard ◽  
Savannah N. Macias ◽  
...  
Keyword(s):  
Dynamic Control ◽  
Genomic Analysis ◽  
Hematopoietic Progenitors ◽  
Cell Fates ◽  
Distinct Cell Type ◽  
Cell Cycle Profile ◽  
Ras Pathway ◽  
Intermediate Progenitors ◽  
Distinct Cell ◽  
Unique Cell

ABSTRACT Genetic and genomic analysis in Drosophila suggests that hematopoietic progenitors likely transition into terminal fates via intermediate progenitors (IPs) with some characteristics of either, but perhaps maintaining IP-specific markers. In the past, IPs have not been directly visualized and investigated owing to lack of appropriate genetic tools. Here, we report a Split GAL4 construct, CHIZ-GAL4, that identifies IPs as cells physically juxtaposed between true progenitors and differentiating hemocytes. IPs are a distinct cell type with a unique cell-cycle profile and they remain multipotent for all blood cell fates. In addition, through their dynamic control of the Notch ligand Serrate, IPs specify the fate of direct neighbors. The Ras pathway controls the number of IP cells and promotes their transition into differentiating cells. This study suggests that it would be useful to characterize such intermediate populations of cells in mammalian hematopoietic systems.

scholarly journals Intermediate Progenitor cells provide a transition between hematopoietic progenitors and their differentiated descendants

2020 ◽  
Author(s):  
Carrie M. Spratford ◽  
Lauren M. Goins ◽  
Fangtao Chi ◽  
Juliet R. Girard ◽  
Savannah N. Macias ◽  
...  
Keyword(s):  
Dynamic Control ◽  
Genomic Analysis ◽  
Hematopoietic Progenitors ◽  
Cell Fates ◽  
Distinct Cell Type ◽  
Cell Cycle Profile ◽  
Ras Pathway ◽  
Intermediate Progenitors ◽  
Distinct Cell ◽  
Unique Cell

AbstractGenetic and genomic analysis in Drosophila suggests that hematopoietic progenitors likely transition into terminal fates via intermediate progenitors (IPs) with some characteristics of either, but perhaps maintaining IP-specific markers. In the past, IPs have not been directly visualized and investigated due to lack of appropriate genetic tools. Here we report a split-GAL4 construct, CHIZ-GAL4, that identifies IPs as cells physically juxtaposed between true progenitors and differentiating hemocytes. IPs comprise a distinct cell type with a unique cell-cycle profile and they remain multipotent for all blood cell fates. Additionally, through their dynamic control of the Notch ligand, Serrate, IPs specify the fate of direct neighbors. The Ras pathway controls the number of IP cells and promotes their transition into differentiating cells. The split-GAL4 strategy is amenable for adoption in mammalian systems and would be invaluable in assigning trajectories that stem and progenitor populations follow as they develop into mature blood cells.

scholarly journals Interleukin-6 and Leukemia Inhibitory Factor Induction of JunB Is Regulated by Distinct Cell Type-specific Cis-acting Elements

1999 ◽  
Vol 274 (40) ◽  
pp. 28697-28707 ◽  
Author(s):  
Robert M. Tjin Tham Sjin ◽  
Kenneth A. Lord ◽  
Abbas Abdollahi ◽  
Barbara Hoffman ◽  
Dan A. Liebermann
Keyword(s):  
Interleukin 6 ◽  
Leukemia Inhibitory Factor ◽  
Inhibitory Factor ◽  
Cell Type ◽  
Distinct Cell Type ◽  
Cis Acting ◽  
Distinct Cell ◽  
Cell Type Specific

scholarly journals Suppressors and activators of JAK-STAT signaling at diagnosis and relapse of acute lymphoblastic leukemia in Down syndrome

2017 ◽  
Vol 114 (20) ◽  
pp. E4030-E4039 ◽  
Author(s):  
Omer Schwartzman ◽  
Angela Maria Savino ◽  
Michael Gombert ◽  
Chiara Palmi ◽  
Gunnar Cario ◽  
...  
Keyword(s):  
Down Syndrome ◽  
B Cell ◽  
Lymphoblastic Leukemia ◽  
Genomic Analysis ◽  
Loss Of Function ◽  
Genomic Databases ◽  
Ras Pathway ◽  
Signaling Inhibitors ◽  
Direct Targeting ◽  
B Cell Precursors

Children with Down syndrome (DS) are prone to development of high-risk B-cell precursor ALL (DS-ALL), which differs genetically from most sporadic pediatric ALLs. Increased expression of cytokine receptor-like factor 2 (CRLF2), the receptor to thymic stromal lymphopoietin (TSLP), characterizes about half of DS-ALLs and also a subgroup of sporadic “Philadelphia-like” ALLs. To understand the pathogenesis of relapsed DS-ALL, we performed integrative genomic analysis of 25 matched diagnosis-remission and -relapse DS-ALLs. We found that the CRLF2 rearrangements are early events during DS-ALL evolution and generally stable between diagnoses and relapse. Secondary activating signaling events in the JAK-STAT/RAS pathway were ubiquitous but highly redundant between diagnosis and relapse, suggesting that signaling is essential but that no specific mutations are “relapse driving.” We further found that activated JAK2 may be naturally suppressed in 25% of CRLF2pos DS-ALLs by loss-of-function aberrations in USP9X, a deubiquitinase previously shown to stabilize the activated phosphorylated JAK2. Interrogation of large ALL genomic databases extended our findings up to 25% of CRLF2pos, Philadelphia-like ALLs. Pharmacological or genetic inhibition of USP9X, as well as treatment with low-dose ruxolitinib, enhanced the survival of pre-B ALL cells overexpressing mutated JAK2. Thus, somehow counterintuitive, we found that suppression of JAK-STAT “hypersignaling” may be beneficial to leukemic B-cell precursors. This finding and the reduction of JAK mutated clones at relapse suggest that the therapeutic effect of JAK specific inhibitors may be limited. Rather, combined signaling inhibitors or direct targeting of the TSLP receptor may be a useful therapeutic strategy for DS-ALL.

scholarly journals Ras is required for a limited number of cell fates and not for general proliferation in Caenorhabditis elegans.

1997 ◽  
Vol 17 (5) ◽  
pp. 2716-2722 ◽  
Author(s):  
J Yochem ◽  
M Sundaram ◽  
M Han
Keyword(s):  
Caenorhabditis Elegans ◽  
Cell Fate ◽  
Cellular Proliferation ◽  
Duct Cell ◽  
Small Gtpase ◽  
Cell Fates ◽  
Larval Stages ◽  
Culture Cells ◽  
Genetic Mosaic ◽  
Distinct Cell

Experiments with mammalian tissue culture cells have implicated the small GTPase Ras in the control of cellular proliferation. Evidence is presented here that this is not the case for a living animal, the nematode Caenorhabditis elegans: proliferation late in embryogenesis and throughout the four larval stages is not noticeably affected in animals lacking Ras in various parts of their cell lineages. Instead, genetic mosaic analysis of the let-60 gene suggests that Ras is required only, at least later in development (a maternal effect cannot be excluded), for establishment of a few temporally and spatially distinct cell fates. Only one of these, the duct cell fate, appears to be essential for viability.

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