Regulation of interstitial cell differentiation in Hydra attenuata. V. Inability of regenerating head to support nematocyte differentiation

1978 ◽  
Vol 34 (1) ◽  
pp. 39-52
Author(s):  
M.S. Yaross ◽  
H.R. Bode
Keyword(s):  
Stem Cell ◽  
Cell Differentiation ◽  
Interstitial Cell ◽  
Irreversible Change ◽  
Cellular Kinetics ◽  
Hydra Attenuata ◽  
Cell Commitment ◽  
Head Regeneration

Nematocyte differentiation was examined during head regeneration in Hydra attenuata. Nematocyte precursors were found to decrease in head-regenerating tissue. This decrease could not be attributed to decreased stem cell commitment or to altered cellular kinetics. The nematocyte precursors could be ‘rescued’ by regrafting a head onto the initially regenerating tissue only prior to the time at which head determination occurred. These results suggest that concurrent with head determination an irreversible change occurs in the tissue environment, resulting in decreased survival of cells committed to nematocyte differentiation.

scholarly journals Regulation of interstitial cell differentiation in Hydra attenuata. IV. Nerve cell commitment in head regeneration is position-dependent

1978 ◽  
Vol 34 (1) ◽  
pp. 27-38
Author(s):  
M.S. Yaross ◽  
H.R. Bode
Keyword(s):  
Stem Cell ◽  
Cell Differentiation ◽  
Nerve Cell ◽  
Interstitial Cell ◽  
Fold Increase ◽  
Nerve Cells ◽  
Multipotent Stem Cell ◽  
Hydra Attenuata ◽  
Cell Commitment ◽  
Head Regeneration

In hydra, nerve cells are a differentiation product of the interstitial cell, a multipotent stem cell. Nerve cell commitment was examined during head regeneration in Hydra attenuata. Within 3 h of head removal there is a 10- to 20-fold increase in nerve cell commitment in the tissue which subsequently forms the new head. Nerve cell commitment is unaltered in the remainder of the gastric region. This local increase in nerve cell commitment is responsible for about one half the new nerve cells formed during head regeneration, while one half differentiate from interstitial cells that migrate into the regenerating tip.

Regulation of interstitial cell differentiation in Hydra attenuata. I. Homeostatic control of interstitial cell population size

1976 ◽  
Vol 20 (1) ◽  
pp. 29-46 ◽  
Author(s):  
H.R. Bode ◽  
K.M. Flick ◽  
G.S. Smith
Keyword(s):  
Cell Differentiation ◽  
Epithelial Cells ◽  
Population Size ◽  
Cell Population ◽  
Interstitial Cell ◽  
Normal Population ◽  
Cell Types ◽  
Hydra Attenuata ◽  
I Cells ◽  
Continuous Labelling

Mechanisms regulating the population size of the multipotent interstitial cell (i-cell) in Hydra attenuata were investigated. Treatment of animals with 3 cycles of a regime of 24 h in 10-2 M hydroxyurea (HU) alternated with 12 h in culture medium selectively killed 95–99% of the i-cells, but had little effect on the epithelial cells. The i-cell population recovered to the normal i-cell:epithelial cell ratio of I:I within 35 days. Continuous labelling experiments with [3H]thymidine indicate that the recovery of the i-cell population is not due to a change in the length of the cell cycle of either the epithelial cells or the interstitial cells. In control animals 60% of the i-cell population undergo division daily while 40% undergo differentiation. Quantification of the cell types of HU-treated animals indicates that a greater fraction of the i-cells were dividing and fewer differentiating into nematocytes during the first 2 weeks of the recovery after HU treatment. Therefore, the mechanism for recovery involves a shift of the 60:40 division:differentiation ratio of i-cells towards a higher fraction in division until the normal population size of the i-cells is regained. This homeostatic mechanism represents one of the influences affecting i-cell differentiation.

Regulation of interstitial cell differentiation in Hydra attenuata. VI. Positional pattern of nerve cell commitment is independent of local nerve cell density

1981 ◽  
Vol 52 (1) ◽  
pp. 85-98
Author(s):  
S. Heimfeld ◽  
H.R. Bode
Keyword(s):  
Cell Density ◽  
Nerve Cell ◽  
Interstitial Cell ◽  
Cell Types ◽  
Nerve Cells ◽  
The Body ◽  
Hydra Attenuata ◽  
Cell Densities ◽  
Cell Commitment ◽  
Body Column

The interstitial cell of hydra is a multipotent stem cell, which produces nerve cells as one of its differentiated cell types. The amount of interstitial cell commitment to nerve differentiation varies in an axially dependent pattern along the body column. The distribution of nerve cell density has the same equivalent axial pattern. These facts have led to speculation that the regulation of nerve cell commitment is dictated by the nerve cell density. We examined this question by assaying interstitial cell commitment behaviour in 2 cases where the normal nerve cell density of the tissue had been perturbed: (1) in epithelial hydra in which no nerve cells were present; and (2) in hydra derived from regenerating-tip isolates in which the nerve density was increased nearly 4-fold. We found no evidence of regulation of nerve cell commitment in response to the abnormal nerve cell densities. However, the typical axial pattern of nerve commitment was still obtained in both sets of experiments, which suggests that interstitial cell commitment to nerve differentiation is dependent on some parameter of axial location that is not associated directly with the local nerve cell density.

scholarly journals Clinical Evidence Against the Continuum of Low-Primed Uncommitted Hematopoietic and Progenitor Cells (CLOUD-HSPC) Concept for Hematopoiesis

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 4860-4860
Author(s):  
Ramon Mohanlal ◽  
Douglas W. Blayney ◽  
Lan Huang
Keyword(s):  
Stem Cell ◽  
Cell Differentiation ◽  
Progenitor Cells ◽  
Clinical Evidence ◽  
Pearson Correlation ◽  
Classical Model ◽  
Stem Cell Differentiation ◽  
Mature Cell ◽  
Cell Counts ◽  
Cell Commitment

Introduction: The classical model of blood stem cell differentiation is branch-like linear HSPC progression from progenitor multi/oligo potent stem cells to differentiated mature cell types. An alternative model, referred to as CLOUD-HSPC, proposes bone marrow (BM) HSPCs continuous and direct differentiation into unipotent cells of myeloid lineage (neutrophils (N), basophils (B), eosinophils (E), monocytes (M), mast cells, megakaryocytes (platelets) and erythrocytes without linear stem cell commitment (Velten Nat Cell Biol 2017). Pegfilgrastim (Peg), and the non-colony stimulating agent Plinabulin (Plin) prevent chemotherapy (chemo) induced neutropenia (CIN) in cancer patients (pts), and both exert BM effects leading to CD34+ cell mobilization (Blayney ASH 2017, 2018). In mice, Plin enhances LSK (Lin-Sca+cKit3+) cell differentiation in BM (Ghosh, AACR 2018). Here we clinically validated the CLOUD-HSPC concept by analyzing peripheral blood mononuclear cell (PBMC) counts derived from two bifurcating progenitor cells 1. Granulocyte-Monocyte Progenitor (GMP) producing N,M,E and B and 2. Common Lymphoid Progenitor (CLP) producing lymphocytes (L), after exposure to Peg or Plin in a CIN setting. With linear stem cell commitment, increase in the differentiated mature cell counts would positively inter-correlate, and with CLOUD-HSPC, they would not. Methods: In the Phase 3 portion of study BPI-2358-105 (NCT03102606), pts with NSCLC, BC or HRPC received pre-medication with dexamethasone (Dex) on day (D) -1,0, and 1 and docetaxel (Doc) on day (D) 1. Pts were randomized 1:1 to either Plin 40 mg (n=52), given 30 min after Doc infusion D1, or Peg 6 mg (n=53), D2. Central laboratory (Covance Laboratory) PBMC counts were obtained at screening, D 1,2, 6,7,8,9,10, 15 in Cycle 1, and correlated with each other at a pre-planned interim analysis. D1 and D2 data points were omitted due to confounding effects of Dex and demargination. Data of Plin and Peg were combined, since both drugs exert BM effects leading to increased N cell counts and showed similar correlation trends. Results: Maximum increases in % from screening value on D5-D15 of each N,M,E,B and L counts correlated with each other. Pearson correlation coefficients (r) after linear regression and corresponding p-value are summarized below. Conclusions: There is a linear and positive inter-correlation between differentiated mature cells derived from the GMP and CLP lineage, proving strong clinical evidence against CLOUD-HSPC, but in favor of the classical linear commitment model. Table Disclosures Mohanlal: BeyondSpring Pharmaceuticals: Employment. Blayney:BeyondSpring Pharmaceuticals: Research Funding. Huang:BeyondSpring Pharmaceuticals: Employment.

SIRT1 Is Required for Mouse Embroyonic Stem Cell Commitment to Hematopoietic Cell Differentiation.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 811-811
Author(s):  
Xuan Ou ◽  
Hee-Don Chae ◽  
Myung-kwan Han ◽  
Tammi Taylor ◽  
Young-June Kim ◽  
...  
Keyword(s):  
Stem Cell ◽  
Cell Differentiation ◽  
Conflicts Of Interest ◽  
Hematopoietic Cells ◽  
Embryonic Stem ◽  
Embryoid Bodies ◽  
Hematopoietic Cell ◽  
Hematopoietic Differentiation ◽  
Cell Commitment

Abstract Abstract 811 SIRT1 is a conserved NAD-dependent deacetylase that catalyzes deacetylation of acetyl-lysine residues of proteins such as histone and p53. SIRT1 plays an important role in a variety of biological processes including stress resistance, metabolism, differentiation and aging (Rodgers et al, Nature, 2005; 434:113). A role for SIRT1 in mouse (m) embryonic stem cell (ESC) maintenance is only beginning to be elucidated (Han et al, Cell Stem Cell, 2008; 2:241). Here we focus on a role for SIRT1 in differentiation of mESCs into hematopoietic cells. We hypothesized that SIRT1 is involved in mESC commitment to hematopoietic cell differentiation. We first confirmed that SIRT1 is highly expressed in the R1 mESC line. Hemoglobinized embryoid bodies (EBs) formed from SIRT1−/− R1 ESC were greatly decreased in number upon removal of LIF compared with that of wildtype parental (+/+) R1 cells, as assessed by primary differentiation assay. Differences in hemoglobinized cells were confirmed by gene analysis of βH1 globin (embryonic hemoglobin), markers for primitive erythroid cells. Next, the ability of SIRT1−/− ESCs to form primitive and definitive hematopoietic cells was evaluated and we found that primitive erythroid progenitors formed from SIRT1−/− R1 cells were greatly decreased. Moreover, after differentiation of SIRT1 −/− mESC there were also significant decreases in definitive erythroid (BFU-E), granulocyte-macrophage (CFU-GM), and multipotential (CFU-GEMM) progenitors. We next explored hematopoietic differentiation in EBs from SIRT1−/− cells by flow cytometry analysis of expression of surface antigens. CD41 defines the onset of primitive and definitive hematopoiesis in the murine embryo (Ferkowicz et al, Development, 2003; 130(18): 4393-403). There were much fewer CD41+ cells in SIRT1 d7 EBs compared with those in WT d7 EBs. To further investigate a role for SIRT1 in hematopoietic differentiation, SIRT1−/− ESCs were tested in an alternative in vitro hematopoietic system involving use of the OP9 stromal cell line and after ectopically-inducing HOXB4 to expand hematopoietic cell differentiation. Unlike WT cells, cells from day 6 EBs of SIRT1−/− ESCs did not differentiate into hematopoietic clusters, instead forming mesoderm-like colonies. This suggested that the defect in differentiation of SIRT1−/− ESCs into hematopoietic cells is before the onset of primitive erythropoiesis. Vascular endothelial growth factor (VEGF)-responsive blast cell colonies are known to contain both endothelial and hematopoietic precursors. This blast-colony-forming cell (BL-CFC) represents a transient population that is present in EBs between day 2.5 and day 3.5 of differentiation and represents the in vitro equivalent of the hemangioblast and as such, the earliest commitment step in the differentiation of mesoderm to the hematopoietic and endothelial lineages. We therefore assessed the ability of WT and SIRT1−/− cells to give rise to BL-CFC. When compared, SIRT1−/− cells generated significantly reduced number of blast colonies, while more colonies of tightly associated cells were observed than with WT cells in the BL-CFC clonogenic assay. Differentiation of mESC towards mesoderm and hemangioblasts (Blast-colony-forming) within the EBs was assessed by measuring brachyury and flk-1 expression respectively. There was no difference in expression of brachyury. However, flk-1 expression was remarkably reduced in SIRT1−/− EBs compared to +/+ EBs. These results indicated that SIRT1−/− cells differentiate properly into mesoderm, while they have a defect in differentiation into blast colonies. Reintroduction of WT SIRT1 into SIRT1−/− cells rescued the hemoglobinized EB formation of SIRT1−/− cells, suggesting that the defect of hematopoietic commitment is due to deletion of SIRT1, and not to genetic drifting of SIRT1−/− cells. Taken together, these results demonstrate that SIRT1 plays a role in hemangioblast development and the earliest stages of hematopoietic cell commitment. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Cell Cycle Kinetics and Development of Hydra Attenuata

1974 ◽  
Vol 16 (2) ◽  
pp. 359-375 ◽  
Author(s):  
C. N. DAVID ◽  
A. GIERER
Keyword(s):  
Cell Cycle ◽  
Stem Cells ◽  
Stem Cell ◽  
Interstitial Cell ◽  
Flow Model ◽  
Interstitial Cells ◽  
Nerve Cells ◽  
Stem Cell Divisions ◽  
Basal Disk ◽  
Hydra Attenuata

The differentiation of nerve cells and nematocytes in Hydra attenuata has been investigated by labelling interstitial cell precursors with [3H]thymidine and following by autoradiography the appearance of labelled, newly differentiated cells. Nematocyte differentiation occurs only in the gastric region where labelled nematoblasts appear 12 h and labelled nematocytes 72-96 h after addition of [3H]thymidine. Labelled nerves appear in hypostome, gastric region, and basal disk about 18 h after addition of [3H]thymidine. The lag in the appearance of labelled cells includes cell division of the precursor as well as differentiation since nerves and nematocytes have 2n postmitotic nuclear DNA content. A cell flow model is proposed for interstitial cells and their differentiated products. Stem cells occur as single interstitial cells or in pairs. Per cell generation about 60 % of the daughter cells of stem cell divisions remain stem cells and about 40 % differentiate nerves and nematocytes. Nerves differentiate directly from stem cells in about 1 day. Nematocyte differentiation requires 5-7 days including proliferation of a cluster of 4, 8, 16 or 32 interstitial cells and differentiation of a nematocyst capsule in each cell. The numbers of interstitial cells and nematoblasts predicted by the cell flow model from the rates of nerve differentiation (900 nerves/day/ hydra), nematocyte differentiation (1760 nematocyte nests/day/hydra) and stem cell proliferation (stem cell cycle = 24 h), agree with the numbers of these cells observed in hydra. The number of stem cells per hydra is 3000-6000 depending on assumptions about the time of determination. The ratio of nematocyte to nerve differentiation averaged over the whole hydra is 3:1. In the hypostome and basal disk interstitial cell differentiation occurs exclusively to nerve cells while in the gastric region the ratio of nematocyte to nerve differentiation is about 7:1.

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